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.

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).

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.

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.

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"