Oropouche Fever

Infectious Disease MONDO:0000345 Pathograph 21 Show in embeddings browser Arbovirus Infection

Oropouche fever is an emerging, usually self-limiting acute arboviral febrile illness caused by Oropouche virus (OROV), a tri-segmented negative-sense RNA orthobunyavirus of the Simbu serogroup transmitted to humans chiefly by the biting midge Culicoides paraensis. It presents as a dengue-like syndrome of fever, headache, myalgia and arthralgia with a characteristic recurrence of symptoms after apparent recovery; a minority develop aseptic meningitis or meningoencephalitis. The 2023-2024 re-emergence across the Americas brought the first reported deaths (from coagulopathy with liver involvement) and the first evidence of vertical transmission with fetal loss and congenital microcephaly.

Ask OpenScientist

Ask a research question about Oropouche Fever. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

◆

Subtypes

1
Congenital Oropouche syndrome (vertical transmission)
Disease arising from vertical (transplacental) transmission of OROV during pregnancy, manifesting as fetal loss, stillbirth, congenital microcephaly and other CNS malformations. This stratum is defined by the route of acquisition and the fetal rather than the adult phenotype. No distinct MONDO term exists for congenital Oropouche syndrome, so this subtype carries no disease_term; it is a route-of-acquisition stratum rather than a separately coded nosological entity.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission."
Documents a fetal route-of-acquisition stratum distinct from postnatal midge-borne disease.
⚙

Pathophysiology

8
Culicoides Midge Inoculation and Viral Entry
The bite of an infected Culicoides paraensis midge inoculates OROV into the dermis. The Gn/Gc glycoproteins mediate attachment and clathrin-dependent entry into permissive cells, followed by endosomal membrane fusion and cytoplasmic release of the three ribonucleoprotein segments.
Downstream
OROV Genome Replication and Interferon Antagonism
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS In vitro / ex vivo
"the virus primarily enters host cells through clathrin-coated vesicles"
Describes the clathrin-dependent entry mechanism this node asserts.
OROV Genome Replication and Interferon Antagonism
The L-protein RdRp transcribes and replicates the genome in the cytoplasm using a cap-snatching mechanism, N encapsidates the segments, and the M-encoded glycoproteins assemble and bud at the Golgi. The non-structural NSs protein antagonizes the host type I interferon response, permitting early high-titre viraemia; a conserved motif at the NSs carboxy terminus is critical for this interferon-antagonistic activity.
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. NSs-mediated suppression of the host type I interferon response GO:0052170 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves NSs-mediated suppression of the host type I interferon response, annotated with symbiont-mediated suppression of host innate immune response (GO:0052170). GO:0052170 is a biological process from the Gene Ontology.
Downstream
Viraemia and Systemic Inflammatory Response
Show evidence (2 references)
PMID:39351896 SUPPORT REVIEW SYNTHESIS In vitro / ex vivo
"These viral protein-RNA complexes facilitate genome replication and transcription in the cytoplasm of infected cells. Translation occurs via a cap-snatching mechanism"
Describes OROV genome replication and cap-snatching transcription.
PMID:39351896 SUPPORT PRIMARY RESULT In vitro / ex vivo
"the viral NSs protein is an interferon (IFN) antagonist, consistent with other NSs-encoding orthobunyaviruses. We identified a conserved motif at the NSs carboxy terminus critical for this IFN antagonistic activity"
Supports the NSs-mediated type I interferon antagonism claim.
Viraemia and Systemic Inflammatory Response
High-titre viraemia (peaking around day 2 of symptoms) together with innate immune activation drives the acute systemic febrile syndrome of fever, headache, chills, myalgia and arthralgia.
Downstream
Hepatotropic Infection
Central Nervous System Neuroinvasion
Transplacental Vertical Transmission
Fever
Headache
Chills
Myalgia
Arthralgia
Vomiting
Thrombocytopenia
Decreased total leukocyte count
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Human OROV disease, or Oropouche fever, typically begins with a fever ranging from 100.4 to 104 °F, followed by headache, chills, malaise, myalgia and arthralgia"
Links viraemia to the acute febrile syndrome.
Hepatotropic Infection
OROV infects the liver, producing necroinflammatory foci that progress to massive hepatic necrosis when the type I interferon response is lost. This hepatic injury underlies the rare severe and fatal human cases and raises circulating transaminases.
hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
hepatocyte necrosis GO:0008219 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased hepatocyte necrosis, annotated with cell death (GO:0008219). GO:0008219 is a biological process from the Gene Ontology.
Downstream
Systemic Coagulopathy
Elevated hepatic transaminase
Show evidence (1 reference)
PMID:42377030 SUPPORT Model organism
"In both models, OROV causes focal hepatic necrosis in mice, which progresses to massive necrosis and death when the Type I interferon receptor is antagonized."
Mouse models show OROV hepatotropism and the IFN-dependent progression to lethal hepatic necrosis, mirroring the fatal human coagulopathic cases.
Systemic Coagulopathy
Severe coagulopathy with haemorrhage accompanies hepatic injury in the rare fatal cases, resembling severe dengue.
Downstream
Abnormal bleeding
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Both patients also suffered from rapid disease progression, severe coagulopathy, and liver impairment."
The two fatal 2024 cases are described as rapid coagulopathy with liver impairment.
Central Nervous System Neuroinvasion
OROV reaches the central nervous system, producing aseptic meningitis and meningoencephalitis and prolonging the acute phase to 2-4 weeks. In earlier outbreaks viral RNA was recovered from cerebrospinal fluid; the 2025 Panama series instead found CSF consistently negative with virus detectable in urine beyond the acute phase, so the diagnostic specimen is not settled.
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.
Downstream
Meningitis
Viral encephalitis
Show evidence (2 references)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
Reports CNS extension of disease with meningitis/encephalitis.
PMID:42742818 SUPPORT Human clinical
"included ocular motor disturbances such as nystagmus and opsoclonus, cerebellar signs including ataxia and vertigo, seizures, altered mental status, and meningeal irritation"
A 2025 Panama case series documents the neurological spectrum.
Transplacental Vertical Transmission
Maternal viraemia leads to hematogenous transplacental infection of the fetoplacental unit and fetal multi-organ infection, with neurotropic damage to the developing fetal brain.
Downstream
Fetal Neurodevelopmental Injury
Show evidence (2 references)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission."
Documents transplacental transmission with fetal multi-organ infection.
PMID:42896562 SUPPORT Human clinical
"Fetal loss and haemorrhage risk were three times higher in women with confirmed infection than in those with no infection"
A prospective cohort quantifies the elevated fetal-loss risk with confirmed maternal OROV infection, the clinical outcome of this branch.
Fetal Neurodevelopmental Injury
OROV infection of the developing fetal brain causes massive neural cell death, neuroinflammation, microglial activation and neutrophil infiltration, with neurodevelopmental disruption, microcephaly and fetal death.
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.
microglial cell activation GO:0001774 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves microglial cell activation (GO:0001774). GO:0001774 is a biological process from the Gene Ontology.
Downstream
Microcephaly
Show evidence (1 reference)
PMID:42811037 SUPPORT Model organism
"Infected embryos present with multi-organ pathology, pneumonitis, myocarditis, steatohepatitis and severe neuropathology, including microcephaly, ventriculomegaly and neural loss."
A Swiss-mouse placental-inoculation model reproduces congenital OROV disease with microcephaly and neural loss.
⬡

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 Oropouche Fever Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

14
Blood 3
Abnormal bleeding HP:0001892 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal bleeding (HP:0001892). HP:0001892 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Severe symptoms can include vomiting and bleeding, such as petechiae, epistaxis and gingival bleeding."
Reports the haemorrhagic phenotype.
Thrombocytopenia HP:0001873 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Thrombocytopenia (HP:0001873). HP:0001873 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
Thrombocytopenia is a common laboratory finding.
Decreased total leukocyte count HP:0001882 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Leukopenia, annotated with Decreased total leukocyte count (HP:0001882). HP:0001882 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
Leukopenia is a common laboratory finding.
Digestive 1
Vomiting 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:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Severe symptoms can include vomiting and bleeding, such as petechiae, epistaxis and gingival bleeding."
Vomiting occurs among more severe symptoms.
Head and Neck 1
Microcephaly HP:0000252 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Microcephaly (HP:0000252). HP:0000252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"has now identified OROV IgM antibodies in serum (two cases) and the CSF (two cases) in three 1-day and one 27-day-old newborn with microcephaly"
Links OROV vertical transmission to neonatal microcephaly.
Immune 2
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:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
Meningitis is a recognized CNS complication.
Viral encephalitis HP:0033993 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Viral encephalitis (HP:0033993). HP:0033993 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
Encephalitis is a recognized CNS complication.
Metabolism 2
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:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Human OROV disease, or Oropouche fever, typically begins with a fever ranging from 100.4 to 104 °F, followed by headache, chills, malaise, myalgia and arthralgia"
Fever is the presenting feature.
Elevated hepatic transaminase Elevated circulating hepatic transaminase concentration HP:0002910 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated liver enzymes, annotated with Elevated circulating hepatic transaminase concentration (HP:0002910). HP:0002910 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
Elevated liver enzymes reflect hepatic involvement.
Nervous System 2
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:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"followed by headache, chills, malaise, myalgia and arthralgia"
Headache is part of the acute syndrome.
Acute demyelinating polyneuropathy HP:0007131 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Guillain-Barre syndrome, annotated with Acute demyelinating polyneuropathy (HP:0007131). HP:0007131 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42058505 SUPPORT REVIEW SYNTHESIS Human clinical
"reports of neurological disease, Guillain-Barré syndrome, adverse pregnancy outcomes, and rare fatalities highlight uncertainties regarding pathogenicity"
The review lists Guillain-Barre syndrome among OROV complications.
Constitutional 3
Chills HP:0025143 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chills (HP:0025143). HP:0025143 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"followed by headache, chills, malaise, myalgia and arthralgia"
Chills accompany the febrile onset.
Myalgia HP:0003326 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myalgia (HP:0003326). HP:0003326 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"followed by headache, chills, malaise, myalgia and arthralgia"
Myalgia is a cardinal feature.
Arthralgia HP:0002829 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arthralgia (HP:0002829). HP:0002829 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"followed by headache, chills, malaise, myalgia and arthralgia"
Arthralgia is part of the dengue-like presentation.
💊

Medical Actions

1
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
No antivirals or vaccines are licensed for OROV; management is supportive. CDC guidance (August 2024) advises against non-steroidal anti-inflammatory drugs in suspected cases until dengue is excluded, to reduce bleeding risk, and recommends that pregnant individuals reconsider non-essential travel to affected areas.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"No antivirals or vaccines are available for OROV, and clinical management is limited to supportive care."
States that only supportive care is available.
🔬

Diagnosis

1
Molecular and serological diagnosis
Confirmation is by RT-qPCR on acute serum (OROV RNA is also detectable in saliva and urine for up to 5 days after onset), with IgM/IgG serology and plaque-reduction neutralization. Because the dengue-like presentation overlaps dengue, Zika and chikungunya, laboratory confirmation is essential to distinguish Oropouche fever from the co-circulating arboviruses.
Show evidence (3 references)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Molecular diagnostics such as RT-qPCR assays are probably more common now and can screen for multiple arboviruses"
RT-qPCR is the common molecular diagnostic.
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Reports of OROV being detectable in saliva and urine up to 5 days after symptom onset may also allow for alternative ways of OROV screening"
Saliva and urine are alternative RT-qPCR specimens within the acute window.
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"The clinical manifestations of OROV closely resemble those of other arboviral infections, such as dengue."
Supports the dengue differential that makes laboratory confirmation necessary.
📈

Progression

3
Incubation period
Incubation: 3-10 days
Abrupt febrile onset follows a 3-10 day incubation; viraemia peaks around day 2 of symptoms.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"The incubation period is 3 to 10 days, with viraemia peaking on day 2 after symptom onset."
Gives the incubation window and viraemia peak.
Acute phase
The acute phase usually lasts 2-7 days; in cases with CNS involvement it can extend to 2-4 weeks.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"The acute phase usually lasts 2 to 7 days, but in cases involving the central nervous system (CNS), it can extend up to 2-4 weeks"
Describes acute-phase duration.
Symptom recurrence
Recurrence of symptoms 2-10 days after the acute phase is characteristic, so the course is often biphasic; virus is not recoverable during recurrence and the cause is unclear.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"Symptom recurrence is common, often occurring about 2-10 days after the acute phase"
Documents the characteristic relapsing course.
📊

Prevalence

1
Americas, 2024 outbreak (confirmed, through end August 2024)
Cases/families reported in the literature Unknown
9852 confirmed cases by the end of August 2024, including five vertical transmission cases and the first two reported deaths.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"As of the end of August 2024, 9852 OROV cases have been confirmed."
Reports the confirmed 2024 outbreak case count.
🦠

Infectious Agent

1
Oropouche virus
Tri-segmented (S, M, L), single-stranded negative-sense RNA virus of the family Peribunyaviridae, genus Orthobunyavirus (Simbu serogroup). The S segment encodes the nucleoprotein N and the non-structural NSs; the M segment encodes the Gn/Gc glycoprotein precursor and NSm; the L segment encodes the RNA-dependent RNA polymerase.
Oropouche virus NCBITaxon:118655 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:39351896 SUPPORT Other
"OROV is a tri-segmented, single-stranded, negative-sense RNA virus within the Peribunyaviridae family and Orthobunyavirus genus"
The review states the agent's taxonomy and genome organization.
↔️

Transmission

2
Culicoides paraensis midge bite transmission
In the urban/epidemic cycle OROV is transmitted to humans by the bite of an infected Culicoides paraensis biting midge. Competence of other vectors (Culex, Aedes spp.) is not established.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"When OROV spills over into humans, it can initiate an urban cycle where the likely vector is the biting midge Culicoides paraensis"
The review names the principal urban vector.
Vertical (transplacental) transmission
During the 2023-2024 re-emergence, maternal OROV infection in pregnancy was shown to transmit vertically to the fetus, with viral RNA recovered from umbilical cord blood and fetal tissues.
Show evidence (1 reference)
PMID:39351896 SUPPORT REVIEW SYNTHESIS Human clinical
"vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission."
Documents the first confirmed vertical transmission.
{ }

Source YAML

click to show 
name: Oropouche Fever
creation_date: "2026-11-04T01:15:28Z"
category: Infectious Disease
description: >-
  Oropouche fever is an emerging, usually self-limiting acute arboviral febrile
  illness caused by Oropouche virus (OROV), a tri-segmented negative-sense RNA
  orthobunyavirus of the Simbu serogroup transmitted to humans chiefly by the
  biting midge Culicoides paraensis. It presents as a dengue-like syndrome of
  fever, headache, myalgia and arthralgia with a characteristic recurrence of
  symptoms after apparent recovery; a minority develop aseptic meningitis or
  meningoencephalitis. The 2023-2024 re-emergence across the Americas brought
  the first reported deaths (from coagulopathy with liver involvement) and the
  first evidence of vertical transmission with fetal loss and congenital
  microcephaly.
disease_term:
  term:
    id: MONDO:0000345
    label: Oropouche fever
  preferred_term: Oropouche fever
synonyms:
- Oropouche virus disease
- Oropouche virus infection
notes: >-
  No GeneReviews chapter exists for Oropouche fever because it is an arboviral infection, not a Mendelian disorder.
parents:
- Arbovirus Infection
infectious_agent:
- name: Oropouche virus
  infectious_agent_term:
    preferred_term: Oropouche virus
    term:
      id: NCBITaxon:118655
      label: Oropouche virus
  description: >-
    Tri-segmented (S, M, L), single-stranded negative-sense RNA virus of the
    family Peribunyaviridae, genus Orthobunyavirus (Simbu serogroup). The S
    segment encodes the nucleoprotein N and the non-structural NSs; the M
    segment encodes the Gn/Gc glycoprotein precursor and NSm; the L segment
    encodes the RNA-dependent RNA polymerase.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "OROV is a tri-segmented, single-stranded, negative-sense RNA virus within the Peribunyaviridae family and Orthobunyavirus genus"
    explanation: The review states the agent's taxonomy and genome organization.
agent_life_cycle:
  description: >-
    OROV is maintained in a sylvatic cycle involving non-human primates and
    pale-throated three-toed sloths (Bradypus tridactylus), with arthropod
    vectors whose sylvatic identity is uncertain; neutralizing antibodies in
    wild and domestic birds raise the possibility of an avian role. When OROV
    spills over into humans it initiates an urban/epidemic cycle whose principal
    vector is the biting midge Culicoides paraensis.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: incidental host (urban cycle)
  - preferred_term: pale-throated three-toed sloth
    term:
      id: NCBITaxon:9354
      label: Bradypus tridactylus
    role: sylvatic reservoir
  vectors:
  - Culicoides paraensis (NCBITaxon:1027879)
transmission:
- name: Culicoides paraensis midge bite transmission
  description: >-
    In the urban/epidemic cycle OROV is transmitted to humans by the bite of an
    infected Culicoides paraensis biting midge. Competence of other vectors
    (Culex, Aedes spp.) is not established.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When OROV spills over into humans, it can initiate an urban cycle where the likely vector is the biting midge Culicoides paraensis"
    explanation: The review names the principal urban vector.
    quote_role: REVIEW_SYNTHESIS
- name: Vertical (transplacental) transmission
  description: >-
    During the 2023-2024 re-emergence, maternal OROV infection in pregnancy was
    shown to transmit vertically to the fetus, with viral RNA recovered from
    umbilical cord blood and fetal tissues.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission."
    explanation: Documents the first confirmed vertical transmission.
    quote_role: REVIEW_SYNTHESIS
pathophysiology:
- name: Culicoides Midge Inoculation and Viral Entry
  biological_scale: MOLECULAR
  description: >-
    The bite of an infected Culicoides paraensis midge inoculates OROV into the
    dermis. The Gn/Gc glycoproteins mediate attachment and clathrin-dependent
    entry into permissive cells, followed by endosomal membrane fusion and
    cytoplasmic release of the three ribonucleoprotein segments.
  downstream:
  - target: OROV Genome Replication and Interferon Antagonism
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the virus primarily enters host cells through clathrin-coated vesicles"
    explanation: Describes the clathrin-dependent entry mechanism this node asserts.
    quote_role: REVIEW_SYNTHESIS
- name: OROV Genome Replication and Interferon Antagonism
  biological_scale: MOLECULAR
  description: >-
    The L-protein RdRp transcribes and replicates the genome in the cytoplasm
    using a cap-snatching mechanism, N encapsidates the segments, and the
    M-encoded glycoproteins assemble and bud at the Golgi. The non-structural
    NSs protein antagonizes the host type I interferon response, permitting
    early high-titre viraemia; a conserved motif at the NSs carboxy terminus is
    critical for this interferon-antagonistic activity.
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  - preferred_term: NSs-mediated suppression of the host type I interferon response
    term:
      id: GO:0052170
      label: symbiont-mediated suppression of host innate immune response
  downstream:
  - target: Viraemia and Systemic Inflammatory Response
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "These viral protein-RNA complexes facilitate genome replication and transcription in the cytoplasm of infected cells. Translation occurs via a cap-snatching mechanism"
    explanation: Describes OROV genome replication and cap-snatching transcription.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the viral NSs protein is an interferon (IFN) antagonist, consistent with other NSs-encoding orthobunyaviruses. We identified a conserved motif at the NSs carboxy terminus critical for this IFN antagonistic activity"
    explanation: Supports the NSs-mediated type I interferon antagonism claim.
    quote_role: PRIMARY_RESULT
- name: Viraemia and Systemic Inflammatory Response
  biological_scale: ORGANISM
  description: >-
    High-titre viraemia (peaking around day 2 of symptoms) together with innate
    immune activation drives the acute systemic febrile syndrome of fever,
    headache, chills, myalgia and arthralgia.
  downstream:
  - target: Hepatotropic Infection
    causal_link_type: DIRECT
  - target: Central Nervous System Neuroinvasion
    causal_link_type: DIRECT
  - target: Transplacental Vertical Transmission
    causal_link_type: DIRECT
  - target: Fever
  - target: Headache
  - target: Chills
  - target: Myalgia
  - target: Arthralgia
  - target: Vomiting
  - target: Thrombocytopenia
  - target: Decreased total leukocyte count
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Human OROV disease, or Oropouche fever, typically begins with a fever ranging from 100.4 to 104 °F, followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Links viraemia to the acute febrile syndrome.
    quote_role: REVIEW_SYNTHESIS
- name: Hepatotropic Infection
  biological_scale: TISSUE
  description: >-
    OROV infects the liver, producing necroinflammatory foci that progress to
    massive hepatic necrosis when the type I interferon response is lost. This
    hepatic injury underlies the rare severe and fatal human cases and raises
    circulating transaminases.
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  biological_processes:
  - preferred_term: hepatocyte necrosis
    term:
      id: GO:0008219
      label: cell death
    modifier: INCREASED
  downstream:
  - target: Systemic Coagulopathy
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Elevated hepatic transaminase
  evidence:
  - reference: PMID:42377030
    reference_title: Oropouche virus causes acute hepatitis in mice controlled by type I interferons.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "In both models, OROV causes focal hepatic necrosis in mice, which progresses to massive necrosis and death when the Type I interferon receptor is antagonized."
    explanation: >-
      Mouse models show OROV hepatotropism and the IFN-dependent progression to
      lethal hepatic necrosis, mirroring the fatal human coagulopathic cases.
  notes: Bound to the broad GO term cell death because GO:0070265 necrotic cell death is obsolete, GO:0097300 programmed necrotic cell death would assert regulated necroptosis that the OROV literature here does not establish, and GO:0006915 apoptotic process names a mechanism that the cited hepatic-necrosis evidence does not support.
- name: Systemic Coagulopathy
  biological_scale: ORGANISM
  description: >-
    Severe coagulopathy with haemorrhage accompanies hepatic injury in the rare fatal cases, resembling severe dengue.
  downstream:
  - target: Abnormal bleeding
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both patients also suffered from rapid disease progression, severe coagulopathy, and liver impairment."
    explanation: >-
      The two fatal 2024 cases are described as rapid coagulopathy with liver
      impairment.
    quote_role: REVIEW_SYNTHESIS
- name: Central Nervous System Neuroinvasion
  biological_scale: TISSUE
  description: >-
    OROV reaches the central nervous system, producing aseptic meningitis and
    meningoencephalitis and prolonging the acute phase to 2-4 weeks. In earlier
    outbreaks viral RNA was recovered from cerebrospinal fluid; the 2025 Panama
    series instead found CSF consistently negative with virus detectable in
    urine beyond the acute phase, so the diagnostic specimen is not settled.
  biological_processes:
  - preferred_term: neuroinflammatory response
    term:
      id: GO:0150076
      label: neuroinflammatory response
  downstream:
  - target: Meningitis
  - target: Viral encephalitis
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
    explanation: Reports CNS extension of disease with meningitis/encephalitis.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:42742818
    reference_title: 'Expanding the spectrum of oropouche virus neurological disease: emerging evidence from the 2025 Panama outbreak.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "included ocular motor disturbances such as nystagmus and opsoclonus, cerebellar signs including ataxia and vertigo, seizures, altered mental status, and meningeal irritation"
    explanation: A 2025 Panama case series documents the neurological spectrum.
- name: Transplacental Vertical Transmission
  biological_scale: ORGANISM
  description: >-
    Maternal viraemia leads to hematogenous transplacental infection of the
    fetoplacental unit and fetal multi-organ infection, with neurotropic damage
    to the developing fetal brain.
  downstream:
  - target: Fetal Neurodevelopmental Injury
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission."
    explanation: Documents transplacental transmission with fetal multi-organ infection.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:42896562
    reference_title: 'Oropouche virus infection in pregnant women in Rio de Janeiro, Brazil: a prospective cohort study.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fetal loss and haemorrhage risk were three times higher in women with confirmed infection than in those with no infection"
    explanation: >-
      A prospective cohort quantifies the elevated fetal-loss risk with
      confirmed maternal OROV infection, the clinical outcome of this branch.
- name: Fetal Neurodevelopmental Injury
  biological_scale: TISSUE
  description: >-
    OROV infection of the developing fetal brain causes massive neural cell death, neuroinflammation, microglial activation and neutrophil infiltration, with neurodevelopmental disruption, microcephaly and fetal death.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: microglial cell activation
    term:
      id: GO:0001774
      label: microglial cell activation
  downstream:
  - target: Microcephaly
  evidence:
  - reference: PMID:42811037
    reference_title: Oropouche virus causes severe congenital disease in embryonic mice.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Infected embryos present with multi-organ pathology, pneumonitis, myocarditis, steatohepatitis and severe neuropathology, including microcephaly, ventriculomegaly and neural loss."
    explanation: >-
      A Swiss-mouse placental-inoculation model reproduces congenital OROV
      disease with microcephaly and neural loss.
phenotypes:
- name: Fever
  category: Phenotype
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
    temporality: ACUTE
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Human OROV disease, or Oropouche fever, typically begins with a fever ranging from 100.4 to 104 °F, followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Fever is the presenting feature.
    quote_role: REVIEW_SYNTHESIS
- name: Headache
  category: Phenotype
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Headache is part of the acute syndrome.
    quote_role: REVIEW_SYNTHESIS
- name: Chills
  category: Phenotype
  phenotype_term:
    preferred_term: Chills
    term:
      id: HP:0025143
      label: Chills
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Chills accompany the febrile onset.
    quote_role: REVIEW_SYNTHESIS
- name: Myalgia
  category: Phenotype
  phenotype_term:
    preferred_term: Myalgia
    term:
      id: HP:0003326
      label: Myalgia
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Myalgia is a cardinal feature.
    quote_role: REVIEW_SYNTHESIS
- name: Arthralgia
  category: Phenotype
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by headache, chills, malaise, myalgia and arthralgia"
    explanation: Arthralgia is part of the dengue-like presentation.
    quote_role: REVIEW_SYNTHESIS
- name: Vomiting
  category: Phenotype
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Severe symptoms can include vomiting and bleeding, such as petechiae, epistaxis and gingival bleeding."
    explanation: Vomiting occurs among more severe symptoms.
    quote_role: REVIEW_SYNTHESIS
- name: Abnormal bleeding
  category: Phenotype
  description: >-
    Haemorrhagic manifestations including petechiae, epistaxis and gingival
    bleeding, prominent in the rare severe coagulopathic cases.
  phenotype_term:
    preferred_term: Abnormal bleeding
    term:
      id: HP:0001892
      label: Abnormal bleeding
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Severe symptoms can include vomiting and bleeding, such as petechiae, epistaxis and gingival bleeding."
    explanation: Reports the haemorrhagic phenotype.
    quote_role: REVIEW_SYNTHESIS
- name: Thrombocytopenia
  category: Laboratory
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
    explanation: Thrombocytopenia is a common laboratory finding.
    quote_role: REVIEW_SYNTHESIS
- name: Decreased total leukocyte count
  category: Laboratory
  phenotype_term:
    preferred_term: Leukopenia
    term:
      id: HP:0001882
      label: Decreased total leukocyte count
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
    explanation: Leukopenia is a common laboratory finding.
    quote_role: REVIEW_SYNTHESIS
- name: Elevated hepatic transaminase
  category: Laboratory
  phenotype_term:
    preferred_term: Elevated liver enzymes
    term:
      id: HP:0002910
      label: Elevated circulating hepatic transaminase concentration
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Lymphopaenia, leucopenia, elevated liver enzymes and thrombocytopaenia are common."
    explanation: Elevated liver enzymes reflect hepatic involvement.
    quote_role: REVIEW_SYNTHESIS
- name: Meningitis
  category: Phenotype
  description: >-
    Aseptic meningitis with CSF pleocytosis, part of the neuroinvasive spectrum.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
    explanation: Meningitis is a recognized CNS complication.
    quote_role: REVIEW_SYNTHESIS
- name: Viral encephalitis
  category: Phenotype
  phenotype_term:
    preferred_term: Viral encephalitis
    term:
      id: HP:0033993
      label: Viral encephalitis
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "it can extend up to 2-4 weeks, potentially leading to meningitis or encephalitis"
    explanation: Encephalitis is a recognized CNS complication.
    quote_role: REVIEW_SYNTHESIS
- name: Acute demyelinating polyneuropathy
  category: Phenotype
  description: >-
    Guillain-Barre syndrome has been reported as a post-infectious complication
    following OROV outbreaks; the mechanism is inferred.
  phenotype_term:
    preferred_term: Guillain-Barre syndrome
    term:
      id: HP:0007131
      label: Acute demyelinating polyneuropathy
  evidence:
  - reference: PMID:42058505
    reference_title: 'Oropouche virus: transmission, epidemiology, genetic diversity, and public health implications.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "reports of neurological disease, Guillain-Barré syndrome, adverse pregnancy outcomes, and rare fatalities highlight uncertainties regarding pathogenicity"
    explanation: The review lists Guillain-Barre syndrome among OROV complications.
    quote_role: REVIEW_SYNTHESIS
- name: Microcephaly
  category: Phenotype
  subtype: Congenital
  description: >-
    Congenital microcephaly following vertical transmission, with OROV IgM
    detected in neonatal serum and CSF.
  phenotype_term:
    preferred_term: Microcephaly
    term:
      id: HP:0000252
      label: Microcephaly
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "has now identified OROV IgM antibodies in serum (two cases) and the CSF (two cases) in three 1-day and one 27-day-old newborn with microcephaly"
    explanation: Links OROV vertical transmission to neonatal microcephaly.
    quote_role: REVIEW_SYNTHESIS
has_subtypes:
- name: Congenital
  display_name: Congenital Oropouche syndrome (vertical transmission)
  description: >-
    Disease arising from vertical (transplacental) transmission of OROV during
    pregnancy, manifesting as fetal loss, stillbirth, congenital microcephaly
    and other CNS malformations. This stratum is defined by the route of
    acquisition and the fetal rather than the adult phenotype. No distinct MONDO
    term exists for congenital Oropouche syndrome, so this subtype carries no
    disease_term; it is a route-of-acquisition stratum rather than a separately
    coded nosological entity.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: vRNA was detected in the umbilical cord blood and various foetal tissues, including the foetal brain, liver, kidneys, lungs, heart and spleen. This is now the first confirmed case of OROV vertical transmission.
    explanation: Documents a fetal route-of-acquisition stratum distinct from postnatal midge-borne disease.
diagnosis:
- name: Molecular and serological diagnosis
  description: >-
    Confirmation is by RT-qPCR on acute serum (OROV RNA is also detectable in
    saliva and urine for up to 5 days after onset), with IgM/IgG serology and
    plaque-reduction neutralization. Because the dengue-like presentation
    overlaps dengue, Zika and chikungunya, laboratory confirmation is essential
    to distinguish Oropouche fever from the co-circulating arboviruses.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Molecular diagnostics such as RT-qPCR assays are probably more common now and can screen for multiple arboviruses"
    explanation: RT-qPCR is the common molecular diagnostic.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Reports of OROV being detectable in saliva and urine up to 5 days after symptom onset may also allow for alternative ways of OROV screening"
    explanation: Saliva and urine are alternative RT-qPCR specimens within the acute window.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The clinical manifestations of OROV closely resemble those of other arboviral infections, such as dengue."
    explanation: Supports the dengue differential that makes laboratory confirmation necessary.
    quote_role: REVIEW_SYNTHESIS
treatments:
- name: Supportive Care
  description: >-
    No antivirals or vaccines are licensed for OROV; management is supportive.
    CDC guidance (August 2024) advises against non-steroidal anti-inflammatory
    drugs in suspected cases until dengue is excluded, to reduce bleeding risk,
    and recommends that pregnant individuals reconsider non-essential travel to
    affected areas.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No antivirals or vaccines are available for OROV, and clinical management is limited to supportive care."
    explanation: States that only supportive care is available.
    quote_role: REVIEW_SYNTHESIS
progression:
- phase: Incubation period
  incubation_days: "3-10"
  notes: >-
    Abrupt febrile onset follows a 3-10 day incubation; viraemia peaks around
    day 2 of symptoms.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The incubation period is 3 to 10 days, with viraemia peaking on day 2 after symptom onset."
    explanation: Gives the incubation window and viraemia peak.
    quote_role: REVIEW_SYNTHESIS
- phase: Acute phase
  notes: >-
    The acute phase usually lasts 2-7 days; in cases with CNS involvement it can
    extend to 2-4 weeks.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The acute phase usually lasts 2 to 7 days, but in cases involving the central nervous system (CNS), it can extend up to 2-4 weeks"
    explanation: Describes acute-phase duration.
    quote_role: REVIEW_SYNTHESIS
- phase: Symptom recurrence
  notes: >-
    Recurrence of symptoms 2-10 days after the acute phase is characteristic, so
    the course is often biphasic; virus is not recoverable during recurrence and
    the cause is unclear.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Symptom recurrence is common, often occurring about 2-10 days after the acute phase"
    explanation: Documents the characteristic relapsing course.
    quote_role: REVIEW_SYNTHESIS
prevalence:
- population: Americas, 2024 outbreak (confirmed, through end August 2024)
  measure_type: CASES_IN_LITERATURE
  notes: >-
    9852 confirmed cases by the end of August 2024, including five vertical
    transmission cases and the first two reported deaths.
  evidence:
  - reference: PMID:39351896
    reference_title: 'Oropouche Virus: An Emerging Orthobunyavirus.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "As of the end of August 2024, 9852 OROV cases have been confirmed."
    explanation: Reports the confirmed 2024 outbreak case count.
    quote_role: REVIEW_SYNTHESIS
  prevalence_class: UNKNOWN
datasets:
📚

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: Oropouche Fever · 2026-11-04T01:43:13Z · View source

Created Oropouche Fever (MONDO:0000345), an emerging Culicoides-borne orthobunyavirus arbovirosis. Deep research via claude_code provider. Modelled causal chain from Culicoides inoculation and NSs IFN-antagonism through viraemia to three branches: hepatotropism/coagulopathy (PMID:42377030 mouse models), CNS neuroinvasion (PMID:42742818 Panama case series), and transplacental vertical transmission to fetal neurodevelopmental injury (PMID:42811037 embryonic-mouse model; PMID:42896562 pregnancy cohort). Phenotypes, agent/transmission/life-cycle, progression (biphasic recurrence), 2024 outbreak prevalence, supportive-care treatment. Term confabulations in the DR report (NCBITaxon:71617 'Culicoides', NCBITaxon:161674 'sloth', HP:0007177 'GBS') were caught by report term-validation and re-looked-up independently; bindings use NCBITaxon:118655, NCBITaxon:1027879, NCBITaxon:9354 and HP:0007131. Validated: just validate (schema+terms+37/37 snippets), entity-refs, causal-targets, granularity (deterministic classes clean), coarse/qualifier/logical/enum/duplicate-key gates, snippet-length/title/grading/reference-titles. preflight-dr SKIP (no causal gene; infectious). Self red-team review (fresh-context subagent) applied before PR: fixed a double-negated modifier on the NSs IFN-antagonism node, rebound the liver-enzyme phenotype from the ALT-specific HP:0031964 to the broader HP:0002910, replaced a timing snippet with the clathrin-entry quote on the entry node, split the hepatotropic node into TISSUE infection and ORGANISM coagulopathy, wired 14/15 phenotypes into the pathograph (GBS left disconnected as post-infectious autoimmunity), added a diagnosis section and a vertical-transmission route.

Claude Code ▸
Oropouche Fever — Disease Characteristics Research Report
claude-haiku-5-5, claude-opus-4-8, claude-opus-5-5 12 citations 2026-11-04T01:21:28.793140

Oropouche Fever — Disease Characteristics Research Report

Target: Oropouche Fever | MONDO:0000345 | Category: Infectious Disease Causal gene: None — this is an arboviral infectious disease, not a Mendelian disorder. The "causal factor" is the Oropouche virus (OROV), a segmented negative-sense RNA orthobunyavirus (NCBITaxon:118655; species Orthobunyavirus oropoucheense). There is no human causal gene; host genetics are at most minor modifiers.

Primary anchor references used throughout: Tilston-Lunel NL, J Gen Virol 2024 (PMID:39351896, PMC11443551) — the current comprehensive review; Schwartz DA, Dashraath P, Baud D, Viruses 2024 (PMID:39339911, PMC11437435) — pregnancy/vertical transmission; and a 2026 New Microbes and New Infections systematic review of 1975–2025 data (DOI 10.1016/j.nmni.2026.100296).

1. Disease Information

Oropouche fever is an emerging, usually self-limiting, acute arboviral febrile illness caused by Oropouche virus, transmitted to humans chiefly by the biting midge Culicoides paraensis. It presents as a dengue-like syndrome (fever, headache, myalgia, arthralgia) with a characteristic relapse/recurrence of symptoms after apparent recovery, and in a minority of cases causes aseptic meningitis or meningoencephalitis. The 2023–2024 re-emergence across the Americas added the first reported deaths and the first evidence of vertical transmission with fetal loss and congenital microcephaly.

Identifiers - MONDO: MONDO:0000345 (Oropouche fever) - ICD-11: 1D4A.0 — Oropouche virus disease (within arthropod-borne viral fevers); ICD-10: A93.0 (Oropouche virus disease) - MeSH: D009894 "Oropouche fever" / supplementary "Oropouche virus" - Pathogen: NCBITaxon:118655 (Oropouche virus); species Orthobunyavirus oropoucheense - OMIM: not applicable (no Mendelian gene)

Synonyms: Oropouche virus disease; Oropouche virus infection; OROV disease; "Oropouche" is from the Oropouche River / wetland region of Trinidad, where the first isolate was obtained in 1955 (etymology: PMC5938780).

Data basis: Aggregated disease-level resources (outbreak surveillance, case series, systematic reviews) rather than EHR-derived individual-patient data; much of the quantitative detail comes from Brazilian and Peruvian outbreak investigations.

Sources: J Gen Virol 2024 / PMC11443551; systematic review / ScienceDirect.

2. Etiology

Primary cause — infectious. OROV, a tri-segmented negative-sense ssRNA virus of family Peribunyaviridae, genus Orthobunyavirus (Simbu serogroup). Infection follows the bite of an infected Culicoides paraensis midge (urban/epidemic cycle); a sylvatic cycle involves non-human primates, sloths and possibly birds.

Risk factors (environmental/ecological — no genetic risk loci established): - Residence in / travel to endemic Amazonian and Latin American regions; northern Brazil accounts for >80% of cases, with Amazonas the likely epicentre (PMID:39351896). - Rainy season — outbreaks show seasonal behaviour with higher incidence in the wet season (Peru 2024–2025, PMC12845246). - Proximity to midge breeding sites (decaying vegetation, banana/cacao plantations, wetlands); deforestation and urbanization bridging sylvatic and urban cycles. - Age 20–49 most affected — attributed to greater occupational/outdoor vector exposure, not biological susceptibility; both sexes equally affected (PMID:39351896). - Pregnancy is a risk factor for severe outcome (fetal, not necessarily maternal).

Protective factors: Vector avoidance (repellents, fine-mesh screening — midges are small enough to pass standard mosquito netting), vector control, and prior infection conferring presumed homotypic immunity. No protective genetic variants described.

Gene–environment interactions: None characterized in humans. In model systems, host type I interferon status is the dominant determinant of outcome (see §6).

Sources: PMC11443551; Peru outbreak PMC12845246.

3. Phenotypes (with suggested HPO terms)

From the 2025/2026 systematic review (1975–2025) and PMID:39351896. Frequencies are approximate and vary by outbreak.

Phenotype Type Frequency HPO suggestion
Fever (often abrupt, high) Symptom/sign ~94% HP:0001945 Fever
Headache Symptom ~87% HP:0002315 Headache
Myalgia Symptom ~73% HP:0003326 Myalgia
Arthralgia Symptom common HP:0002829 Arthralgia
Chills/rigors Symptom common HP:0025143 Chills
Malaise/fatigue Symptom common HP:0012378 Fatigue
Nausea / vomiting Symptom frequent in severe HP:0002018 Nausea; HP:0002013 Vomiting
Photophobia Symptom frequent HP:0000613 Photophobia
Retro-orbital/eye pain Symptom frequent HP:0000541 (retinal detachment — not apt); use HP:0025435 Retro-orbital pain if available, else HP:0000481 Abnormal cornea? → prefer HP:0025435
Dizziness/vertigo Symptom in CNS cases HP:0002321 Vertigo
Maculopapular rash Sign variable HP:0000988 Skin rash (or HP:0000509 — n/a)
Lymphopenia Lab common HP:0001888 Lymphopenia
Leukopenia Lab common HP:0001882 Leukopenia
Thrombocytopenia Lab common HP:0001873 Thrombocytopenia
Elevated transaminases Lab common HP:0002910 Elevated hepatic transaminase
Hemorrhage (petechiae, epistaxis, gingival) Sign severe cases HP:0001892 Abnormal bleeding; HP:0000421 Epistaxis; HP:0000225 Gingival bleeding; HP:0000979 Petechiae
Aseptic meningitis Sign ~2% (1980 Pará: 22/292) HP:0011227 Meningitis (→ HP:0100702 Aseptic meningitis if present)
Meningoencephalitis / neck stiffness, nystagmus, lethargy Sign rare HP:0002383 Encephalitis; HP:0031179 Nuchal rigidity; HP:0000639 Nystagmus
Guillain-Barré syndrome (post-infectious) Sign rare, reported post-Cuba outbreak HP:0007177 (acute inflammatory demyelinating polyneuropathy — GBS)

Characteristics - Onset: acute/abrupt, after 3–10 day incubation; adult-predominant by exposure. - Severity: usually mild–moderate and self-limiting; severe coagulopathic/hepatic disease and death are rare (two 2024 deaths, Bahia, in healthy women 21 & 24 y with severe coagulopathy and liver impairment, no neurological signs). - Progression: acute phase 2–7 days, then recurrence of symptoms in ~60% (classically; "common") 2–10 days later, without detectable viraemia — mechanism unknown. - QoL: acute disabling febrile illness causing days–weeks of lost activity; recurrence prolongs morbidity; CNS and congenital cases carry major long-term impact.

Congenital phenotypes (vertical transmission): microcephaly (HP:0000252), stillbirth/fetal death (HP:0001560 fetal death; HP:0500141), congenital malformation syndrome, OROV IgM in neonatal serum/CSF.

Sources: systematic review; PMC11443551; virulence review PMC13134406.

4. Genetic / Molecular Information (viral genome — no human causal gene)

OROV has a tri-segmented, single-stranded, negative-sense RNA genome; virions are enveloped, spherical, ~90–100 nm (PMID:39351896).

Segment Size Encodes Function / GO suggestion
S 958 nt N nucleoprotein (~27 kDa) + NSs (~11 kDa), overlapping ORFs N: ribonucleocapsid (GO:0019013 viral nucleocapsid); NSs: type I interferon antagonist (GO:0039503 suppression of host innate immune response; GO:0039563)
M 4385 nt glycoprotein precursor → Gn (~32 kDa) + Gc (~110 kDa) + NSm (~27 kDa) Gn/Gc: receptor binding & membrane fusion/entry (GO:0019064 fusion of virus membrane with host plasma membrane); NSm dispensable for mammalian replication
L 6852 nt RdRp / L protein (~261 kDa) RNA-dependent RNA polymerase, uses cap-snatching (GO:0039689 negative stranded viral RNA replication; GO:0003968)

Reassortment is central to OROV evolution and epidemiology. Reassortment with related Simbu-group viruses (Madre de Dios, Iquitos, Perdões, possibly Jatobal) has generated novel M segments. The 2023–2024 American lineage is a novel reassortant carrying Amazonian M-segment ancestry; some authors link it to altered clinical behaviour (vertical transmission, deaths) while a Peruvian study found no clear change in clinical/epidemiological behaviour across variants — this remains contested.

Human genetics: No causal genes, pathogenic variants, modifier genes, allele frequencies, or epigenetic signatures are established. Fields 4's human-variant subheadings are not applicable. Host determinant of outcome is the innate antiviral (MAVS–IRF3/7–IFN-α/β) pathway, characterized only in animal/cell models (§6).

Sources: PMC11443551; reassortant pregnancy report PMC11765011.

5. Environmental Information

  • Infectious agent: Oropouche virus (NCBITaxon:118655).
  • Vectors: Urban/epidemic — Culicoides paraensis (biting midge; NCBITaxon:71617 for genus Culicoides) is the principal proven vector; Culicoides sonorensis equally susceptible in lab. Secondary/possible — Culex quinquefasciatus (OROV-positive field midges/mosquitoes found in Mato Grosso, but competence not established; most Aedes/Culex are poorly competent when orally fed). Sylvatic vector unknown; OROV isolated from Mansonia venezuelensis and Aedes serratus.
  • Reservoir hosts: Non-human primates (Callithrix penicillata, Cebus olivaceus), pale-throated three-toed sloth (Bradypus tridactylus); neutralizing antibodies in wild/domestic birds suggest possible avian carriage.
  • Ecological drivers: Deforestation, agricultural expansion (cacao, banana), urbanization, high-density midge breeding in decaying organic matter, and climate/rainfall seasonality.
  • Lifestyle/occupational: Outdoor and agricultural work in endemic zones; no diet/smoking/alcohol associations.

Sources: PMC11443551; vector-competence systematic review PMC12043118.

6. Mechanism / Pathophysiology

Causal chain (initiating exposure → clinical manifestation)

  1. Infected Culicoides paraensis midge bites a human → inoculation of OROV into dermis (sylvatic spillover initiates the urban cycle). Demonstrated epidemiologically.
  2. Gn/Gc glycoproteins mediate attachment and clathrin-dependent entry into permissive cells, followed by endosomal membrane fusion → cytoplasmic release of the three RNP segments. Demonstrated in vitro (Vero, mammalian cells).
  3. L-protein RdRp transcribes/replicates the genome using cap-snatching; N encapsidates; M-encoded glycoproteins assemble at the Golgi → new virions bud and spread. Demonstrated.
  4. NSs antagonizes the host type I interferon response (suppresses host transcription / IFN-α/β induction), permitting early high-titre viraemia (peaks ~day 2 of symptoms). Demonstrated; NSs deletion attenuates the virus.
  5. Viraemia + innate immune activation (pro-inflammatory cytokines) → systemic febrile syndrome (fever, headache, myalgia, arthralgia). Inferred from clinical + model data.
  6. Branch A — hepatotropism/coagulopathy: OROV infects the liver, producing focal → (when IFN is antagonized) massive hepatic necrosis, transaminase elevation, thrombocytopenia and coagulopathy → severe/fatal disease in a minority. Demonstrated in mouse models (anti-IFNAR1 lethal model); consistent with the two 2024 fatal human cases.
  7. Branch B — neurotropism: OROV reaches the CNS (viral RNA in CSF) → aseptic meningitis / meningoencephalitis; prolongs acute phase to 2–4 weeks. Demonstrated (CSF RNA, outbreak meningitis rates).
  8. Branch C — post-infectious autoimmunity: molecular mimicry/immune dysregulation → Guillain-Barré syndrome rise after the Cuban outbreak. Association; mechanism inferred.
  9. Branch D — vertical transmission: maternal viraemia → hematogenous transplacental infection → fetoplacental infection, fetal multi-organ infection, neurotropic fetal CNS damage → microcephaly, fetal death/stillbirth. Demonstrated (fetal-tissue RNA, neonatal IgM); mouse models reproduce severe congenital disease; causality still being consolidated.

Supporting detail

  • Molecular pathways / cellular processes: innate antiviral signalling (RIG-I/MAVS → IRF-3/IRF-7 → type I IFN) restricts OROV; OROV NSs counteracts it. OROV infection induces apoptosis and host translational shutoff (GO:0006915 apoptotic process; GO:0051607 defense response to virus; GO:0045071 negative regulation of viral genome replication).
  • Immune system: type I IFN (IFN-α/β) is the principal restriction factor (MAVS−/−, IRF3/7−/−, IFNAR−/− mice show enhanced, often lethal, infection). Immunocompetent mice are largely resistant — hamsters and IFN-deficient mice are the tractable models.
  • Tissue damage: hepatic necrosis (oxidative/inflammatory), CNS inflammation, placental/fetal infection.
  • Cell types (CL suggestions): hepatocyte (CL:0000182), neuron (CL:0000540), macrophage/monocyte (CL:0000235), trophoblast (CL:0000351) / syncytiotrophoblast, endothelial cell (CL:0000115).

Sources: virulence/pathogenesis review PMC13134406; reporter-virus/IFN pathogenesis, JVI; acute hepatitis mouse model PMC13386938; type I IFN controls vertical transmission, iScience; congenital disease in embryonic mice, Nat Commun.

7. Anatomical Structures Affected (UBERON / GO-CC)

  • Organ level: blood/vasculature (viraemia; UBERON:0000178 blood), liver (UBERON:0002107), central nervous system / brain & meninges (UBERON:0000955 brain; UBERON:0002360 meninges), placenta & fetus (UBERON:0001987 placenta), skin (inoculation site, rash; UBERON:0002097).
  • Body systems: immune/haematologic, hepatic, nervous, and (in pregnancy) fetoplacental; musculoskeletal (myalgia/arthralgia).
  • Tissue/cell: hepatocytes, neurons/glia, meningeal cells, trophoblast, mononuclear phagocytes, endothelium.
  • Subcellular (GO-CC): cytoplasm/ribonucleoprotein complex (GO:0019013), Golgi apparatus (viral assembly/budding; GO:0005794), host plasma/endosomal membranes (entry).
  • Lateralization: systemic/bilateral; no lateralized pattern.

8. Temporal Development

  • Onset: acute, after 3–10 day incubation; abrupt febrile start.
  • Acute phase: 2–7 days; viraemia peaks ~day 2.
  • Recurrence: symptom relapse 2–10 days after acute phase is characteristic ("common"), without detectable virus — course is therefore often biphasic/relapsing rather than monophasic.
  • CNS cases: extended course, 2–4 weeks.
  • Duration: self-limited in the vast majority; full recovery typical. Rare severe (hepatic/coagulopathic) and fatal courses; post-infectious GBS has its own neurologic trajectory.
  • Remission: spontaneous. No chronic infection established.
  • Critical period: pregnancy (fetal vulnerability to vertical transmission) is the key window for adverse outcomes.

Source: PMC11443551.

9. Inheritance and Population (Epidemiology)

  • Not heritable — infectious; inheritance/penetrance/consanguinity/carrier-frequency subheadings are not applicable.
  • Historical burden: first human recognition Trinidad 1955; Brazilian emergence Belém 1960; >30 outbreaks 1961–1996, ~500,000 estimated cases (PMID:39351896). Likely one of the most common arboviral infections in the Amazon, long under-diagnosed.
  • 2024 re-emergence: 9,852 confirmed cases by end of August 2024, including 5 vertical-transmission cases and the first 2 reported deaths; WHO assessed regional/global risk as high.
  • Geography: endemic — northern Brazil (>80% of cases; Amazonas epicentre), Peru, Bolivia, Ecuador, Colombia, Venezuela, Panama, Haiti, French Guiana. 2024 expansion — sustained transmission in non-endemic Brazilian states, Cuba (first time), Dominican Republic; imported/travel cases in the US (≥32 by Aug 2024, mostly Florida, returning from Cuba) and Europe (Italy, Spain, Germany).
  • Demographics: both sexes equally affected; peak ages 20–49 (exposure-driven); no ethnic predisposition.

Sources: PMC11443551; CDC EID Nov 2024.

10. Diagnostics

  • Molecular (confirmatory): RT-qPCR on serum/blood within ~5 days of onset (also detectable in saliva and urine up to 5 days); multiplex arbovirus panels used to distinguish dengue/Zika/chikungunya. (LOINC: use a molecular-detection code for OROV RNA where available.)
  • Viral isolation: on acute samples (≤5-day window), historically in suckling mice/Vero cells — reference labs only.
  • Serology: IgM/IgG ELISA; plaque-reduction neutralization (specific). Older HI/complement-fixation have low specificity and cross-reactivity within the Simbu group.
  • Supportive lab: leukopenia, lymphopenia, thrombocytopenia, elevated transaminases.
  • CSF: pleocytosis and OROV RNA in meningitis/encephalitis.
  • Congenital work-up: OROV RT-PCR of placenta/fetal tissues; neonatal serum/CSF IgM; neuroimaging for microcephaly.
  • Clinical criteria / differential: no formal society criteria; diagnosis is clinical-epidemiological + lab. Differential: dengue, Zika, chikungunya, mayaro, malaria, leptospirosis, other Simbu-group viruses — overlapping dengue-like presentation makes laboratory confirmation essential; the relapsing course is a clinical clue.
  • Screening: no population screening; avoid NSAIDs in suspected cases until dengue excluded (CDC Aug 2024 guidance, bleeding risk).

Source: PMC11443551.

11. Outcome / Prognosis

  • Generally excellent — self-limiting; historically no deaths until the 2024 outbreak (2 fatalities in young healthy women with coagulopathy/hepatic failure).
  • Morbidity: days–weeks of disabling febrile illness; frequent symptom recurrence; aseptic meningitis usually resolves without sequelae.
  • Severe/adverse outcomes: rare hemorrhagic/hepatic/coagulopathic disease; post-infectious Guillain-Barré syndrome; fetal loss (miscarriage, stillbirth) and congenital microcephaly following vertical transmission are the most serious recognized outcomes.
  • Prognostic factors: pregnancy (fetal risk), severe coagulopathy/hepatic involvement, CNS involvement; host IFN competence (from models).
  • Case fatality: historically ~0; very low even in 2024, but true denominators are uncertain due to under-ascertainment.

Sources: PMC11443551; Lancet Infect Dis 2024, vertical transmission & deaths.

12. Treatment (NCIT suggestions)

  • No approved antiviral and no licensed vaccine — management is supportive care only (NCIT:C15747 Supportive Care).
  • Symptomatic: antipyretics/analgesics — acetaminophen/paracetamol preferred; avoid NSAIDs and aspirin until dengue excluded (bleeding risk). Pharmacotherapy (NCIT:C15986) with analgesic agent (acetaminophen CHEBI:46195).
  • Supportive: hydration/fluids, rest; hospital/critical care (NCIT:C53511 Intensive Care) for severe coagulopathic/hepatic or neurologic disease.
  • Pregnancy: vector-bite avoidance and monitoring; no specific therapy.
  • Experimental: no agent in advanced clinical trials; antivirals and vaccine candidates are preclinical. (ClinicalTrials.gov yields no OROV-specific licensed-therapy trial as of 2025–2026.)
  • Pharmacogenomics / targeted / cell / gene / RNA therapies: not applicable.

Source: PMC11443551.

13. Prevention

  • Primary — vector/bite avoidance (mainstay): insect repellents (DEET/picaridin), long sleeves, fine-mesh screening (midges pass standard mosquito nets), avoiding peak midge activity; vector control of Culicoides breeding sites; community education.
  • Immunization: no vaccine available (candidates preclinical).
  • Secondary: early recognition and lab confirmation; arbovirus surveillance; NSAID avoidance pending dengue exclusion.
  • Tertiary: supportive management to prevent complications; obstetric monitoring in infected pregnant people.
  • Pregnancy-specific public health: enhanced bite protection and risk counselling for pregnant travelers to/residents of endemic areas (CDC/PAHO advisories, 2024).
  • Public health: environmental management (reducing organic-debris breeding habitat), reduced deforestation-driven spillover, cross-border surveillance given travel-associated spread.

Sources: PMC11443551; CDC EID 2024.

14. Other Species / Natural Disease

  • Host taxonomy (NCBITaxon): humans (9606); non-human primate reservoirs — Callithrix penicillata, Cebus olivaceus; pale-throated three-toed sloth Bradypus tridactylus (NCBITaxon:161674); wild/domestic birds (serological evidence).
  • Vectors: Culicoides paraensis; genus Culicoides (NCBITaxon:71617).
  • Natural disease in animals: reservoir hosts are generally asymptomatic amplifying hosts; no overt natural disease syndrome is described in sloths/primates — they maintain the sylvatic cycle. No companion-animal disease recognized.
  • Zoonotic/cross-species: classic zoonotic spillover from a sylvatic (animal/arthropod) cycle into humans, with human amplification in the urban cycle. Reassortment among co-circulating Simbu-group orthobunyaviruses (Madre de Dios, Iquitos, Jatobal) is a key cross-lineage feature.

Source: PMC11443551.

15. Model Organisms

  • Mice: the workhorse models require impaired type I IFN — IFNAR−/−, MAVS−/−, IRF-3/IRF-7−/−, and anti-IFNAR1-antibody-treated mice develop productive, often lethal infection with hepatic necrosis and systemic spread; immunocompetent adult mice are largely resistant (sublethal). Suckling mice were the historical isolation host. A ZsGreen reporter OROV (M-segment) enables in vivo pathogenesis tracking. Embryonic/pregnant mouse models reproduce severe congenital disease and fetoplacental infection, with type I IFN controlling vertical transmission.
  • Hamsters: permissive and useful for immune/pathogenesis studies where immunodeficient mice are limiting.
  • Cell lines / in vitro: Vero (isolation/titration), plus mammalian and insect (C6/36) cells; used for entry, NSs–IFN antagonism, and reassortment studies.
  • Recapitulation / limitations: IFN-deficient mice capture hepatotropism, CNS invasion, lethality and congenital disease but depend on removing the very restriction factor (type I IFN) that shapes human disease, so translational fidelity to immunocompetent humans is limited; whether the 2024 reassortant crosses the placenta more efficiently than historical strains is not yet confirmed.
  • Applications: entry/replication, NSs interferon antagonism, tissue tropism (liver, CNS), vertical transmission, antiviral/vaccine preclinical testing.

Sources: reporter virus, JVI; acute hepatitis model, PMC13386938; iScience vertical transmission; Nat Commun congenital disease.

Key citations (for KB evidence items — fetch with just fetch-reference)

  • PMID:39351896 — Tilston-Lunel NL. Oropouche Virus: an emerging orthobunyavirus. J Gen Virol 2024 (comprehensive review; genome, vectors, clinical, epidemiology).
  • PMID:39339911 — Schwartz DA, Dashraath P, Baud D. OROV in pregnancy: placental/fetal infection, stillbirth, microcephaly. Viruses 2024.
  • Systematic review 1975–2025, New Microbes and New Infections — symptom frequencies (ScienceDirect).
  • Lancet Infect Dis 2024 (DOI 10.1016/S1473-3099(24)00557-7) — first vertical transmission & deaths.
  • CDC EID 30(11), Nov 2024 — reemergence and US spread risk.
  • JVI reporter virus / IFN pathogenesis; iScience & Nat Commun congenital models.

Notes for curation

  • This is an infectious disease entry: populate infectious_agent with NCBITaxon:118655 (Oropouche virus), at least one transmission route (vector-borne, Culicoides paraensis; plus hematogenous vertical transmission), and agent_life_cycle with vectors (Culicoides) and non-human reservoirs (primates, sloths) — per the infectious-disease granularity ladder (§3e). Granularity level = named clinical entity (Oropouche fever); do not split by viral lineage/reassortant — carry lineage structurally if needed.
  • No human causal gene / OMIM — leave genetic: empty; the virulence genetics are viral (S/M/L segments, NSs IFN antagonist).
  • Before binding any term or citing any snippet, verify CURIEs with OAK/term validation and fetch each reference into references_cache/ — several HPO suggestions above (e.g. retro-orbital pain, aseptic meningitis) and the symptom-frequency numbers should be confirmed against the fetched sources rather than taken from this report verbatim.

Reference Validation

Checked with linkml-reference-validator 0.5.1.

Outcome Count
References checked 13
Resolved 12
Unresolved (possible confabulation) 1
Unverifiable 0
References weighed for topical relevance 12
On topic 10
Off topic 0

Unresolved references

These identifiers did not resolve to a record and may be fabricated. A lookup that failed for transport reasons is indistinguishable from one that failed because the record does not exist, so spot-check before acting on them:

  • DOI:10.1016/j.nmni.2026.100296 (1 mention) - Identifier did not resolve to a record

Term Validation

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

Outcome Count
Terms checked 61
Resolved 59
Unresolved (possible confabulation) 1
Obsolete 1
Unverifiable 0
Terms whose name was checked 5
Terms named correctly 2
Terms named as a different term 2
Terms whose name is worth a second look 1

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • NCBITaxon:71617 (2 mentions) - the report calls it "Culicoides"; NCBITaxon calls it Tolypocladium ophioglossoides
  • NCBITaxon:161674 (1 mention) - the report calls it "Bradypus tridactylus"; NCBITaxon calls it Tetratrichomonas sp. 1998-5003

Unresolved terms

These identifiers do not exist in an ontology that resolved other terms from the same prefix, so they were most likely invented:

  • HP:0007177 (1 mention), reported as "acute inflammatory demyelinating polyneuropathy — GBS" - HP does not contain this term

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • GO:0039503 (obsolete suppression by virus of host innate immune response) (1 mention) - replaced by GO:0052170

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • NCBITaxon:118655 (4 mentions) - the report calls it "Oropouche virus", "Infectious agent: Oropouche virus"; NCBITaxon calls it Oropouche virus**

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • NCBITaxon:118655 - called "Oropouche virus", "Infectious agent:** Oropouche virus"