Rift Valley Fever

Infectious MONDO:0017880 Pathograph 20 Show in embeddings browser Viral hemorrhagic fever

Rift Valley fever (RVF) is a mosquito-borne, zoonotic viral disease caused by Rift Valley fever virus (RVFV), a tri-segmented negative-sense RNA phlebovirus of the family Phenuiviridae, order Bunyavirales. It is a disease primarily of domestic ruminants in Africa and the Arabian Peninsula, in which it causes abortion storms and high neonatal mortality; humans are infected as an epizootic spillover, chiefly by bites of infected mosquitoes (notably floodwater Aedes, which maintain the virus transovarially, and Culex, which amplify epidemics) and by direct contact with the blood, tissues and aborted materials of viraemic livestock. The great majority of human infections are a self-limiting febrile illness, but a minority progress to one of three severe syndromes - a viral hemorrhagic fever with hepatic necrosis, a delayed retinitis that can cause permanent visual loss, and a meningoencephalitis. Large outbreaks follow periods of heavy rainfall and flooding that expand mosquito populations, which links RVF epidemiology to climate and makes it a recognised emerging and re-emerging arboviral threat. The severe hemorrhagic form converges on the shared vascular and hemostatic lesion of the viral hemorrhagic fevers.

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⚙

Pathophysiology

8
RVFV Replication and NSs-Mediated Interferon Antagonism
After inoculation RVFV replicates in cells at the site of infection and in the liver and spleen. Its non-structural protein NSs is the principal virulence factor: it suppresses host general transcription and blocks induction of type I interferon, allowing unchecked early viral replication and the high viraemia that drives severe disease.
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 type I interferon induction GO:0032480 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased NSs-mediated suppression of type I interferon induction, annotated with negative regulation of type I interferon production (GO:0032480). GO:0032480 is a biological process from the Gene Ontology.
Downstream
High Viremia and Hepatotropic Spread
Show evidence (2 references)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Other
"NSs is known to be a major virulence factor of RVFV"
Identifies NSs as the principal virulence factor of the virus.
PMID:21666766 SUPPORT REVIEW SYNTHESIS In vitro / ex vivo
"NSs induces the shut-down of host transcription, including transcription of both type-I IFN and ISGs mRNAs, to prevent antiviral responses. NSs also induces the degradation of PKR to prevent eIF2α-mediated host and viral translational shut-off"
Supports NSs-mediated suppression of type I interferon induction and the block of interferon-stimulated antiviral responses.
High Viremia and Hepatotropic Spread
Interferon antagonism permits rapid systemic dissemination with high-titre viraemia and preferential infection of the liver, the major target organ, where RVFV replicates chiefly in hepatocytes. The magnitude of viraemia correlates with progression to severe disease.
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.
viral genome replication GO:0019079 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology.
Downstream
Hepatocellular Necrosis
Endothelial Activation and Damage
Hepatitis
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Other
"The liver is the major target organ of RVFV"
Establishes the liver as the principal target organ in RVFV infection.
Hepatocellular Necrosis
Direct viral cytopathology and apoptosis of infected hepatocytes produce the extensive hepatic necrosis that is the pathological hallmark of fatal RVF - diffuse, with the centrilobular area more affected than the portal area - releasing transaminases and impairing synthesis of coagulation factors.
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 apoptotic process GO:0097284 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased hepatocyte apoptotic process (GO:0097284). GO:0097284 is a biological process from the Gene Ontology.
Downstream
Coagulopathy and Disseminated Intravascular Coagulation
Jaundice
Elevated hepatic transaminases
Show evidence (2 references)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"Postmortem examination shows diffuse necrosis of hepatocytes which more greatly affect the centrilobular area than the portal area"
Documents the hepatocellular necrosis with centrilobular predominance that is the pathological hallmark of fatal human RVF.
PMID:21666766 SUPPORT REVIEW SYNTHESIS Model organism
"indicating that RVFV replication induces apoptosis in hepatocytes"
Supports hepatocyte apoptosis as a mechanism of the hepatic necrosis, shown by TUNEL staining in the mouse model.
Endothelial Activation and Damage
Systemic infection and the attendant cytokine response activate and damage the microvascular endothelium. This is the cellular lesion that, in the viral hemorrhagic fevers, drives the increase in vascular permeability downstream.
endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology.
endothelial cell activation GO:0042118 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased endothelial cell activation (GO:0042118). GO:0042118 is a biological process from the Gene Ontology.
Downstream
Increased Vascular Permeability
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Model organism
"hemorrhage was induced by a combination of vascular endothelial damage and an inability to clot blood in response to the damage"
Supports vascular endothelial damage as a contributor to the bleeding diathesis, shown in experimentally infected sheep.
Increased Vascular Permeability
Endothelial activation and damage increase microvascular permeability with plasma leakage - the rate-limiting lesion shared with the other viral hemorrhagic fevers, and the node through which the hemorrhagic form of RVF converges on that syndrome.
regulation of vascular permeability GO:0043114 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased regulation of vascular permeability (GO:0043114). GO:0043114 is a biological process from the Gene Ontology.
Downstream
Coagulopathy and Disseminated Intravascular Coagulation
Hemorrhage
Coagulopathy and Disseminated Intravascular Coagulation
The combination of endothelial injury, impaired hepatic factor synthesis and platelet consumption produces a consumptive coagulopathy and disseminated intravascular coagulation, with falling platelet counts and deranged clotting that drive bleeding and multi-organ failure in severe RVF.
Downstream
Hemorrhage
Thrombocytopenia
Disseminated intravascular coagulation
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"die from renal failure or disseminated intravascular coagulation (DIC) accompanied by an elevation of ALT, AST, LDH or D-Dimer, or a decrease in platelet count"
Documents disseminated intravascular coagulation with raised D-dimer and falling platelets as a fatal pathway in severe human RVF.
Delayed Retinitis
One to three weeks after the acute febrile illness a minority of patients develop a macular and paramacular retinitis with retinal haemorrhage, vasculitis and oedema. It follows rather than accompanies the viraemia and is thought to be largely immune-mediated; macular involvement can leave a permanent central scotoma.
Downstream
Retinal hemorrhage
Vision loss
Show evidence (2 references)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"the affected eyes had macular edema with exudates containing a white mass covering the macular area with or without retinal hemorrhage, vasculitis"
Describes the macular retinitis with retinal haemorrhage and vasculitis that characterises the delayed ocular form.
PMID:12539063 SUPPORT Human clinical
"Sixteen patients had retinitis and 7 patients had meningoencephalitis as late complications in the course of the disease"
Documents retinitis as a late complication in a prospective cohort of severe human RVF, quantifying this delayed ocular form.
Meningoencephalitis
A separate delayed severe syndrome is a meningoencephalitis, appearing days to weeks after the acute phase, with neuronal infection and inflammation presenting as encephalitis with headache, confusion and focal deficits.
Downstream
Encephalitis
Show evidence (2 references)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"A group of RVF patients who died from typical hemorrhagic fever also had encephalitis in addition to hepatic and gastro-intestinal necroses"
Documents meningoencephalitis as a severe neuroinvasive form of human RVF, here co-occurring with the hemorrhagic form.
PMID:12539063 SUPPORT Human clinical
"Sixteen patients had retinitis and 7 patients had meningoencephalitis as late complications in the course of the disease"
Documents meningoencephalitis as a late complication in a prospective cohort of severe human RVF.
⬡

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 Rift Valley 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.
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Phenotypes

12
Blood 4
Hemorrhage 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:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"bleeding from the gums and/or gastrointestinal mucosal membrane"
Documents mucosal bleeding in the hemorrhagic form of human RVF.
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:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"reduction of platelet count and hemoglobin are seen in these patients"
Documents thrombocytopenia (falling platelet count) in severe human RVF.
Disseminated intravascular coagulation HP:0005521 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Disseminated intravascular coagulation (HP:0005521). HP:0005521 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"die from renal failure or disseminated intravascular coagulation (DIC)"
Documents disseminated intravascular coagulation as a fatal outcome of severe human RVF.
Retinal hemorrhage HP:0000573 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Retinal hemorrhage (HP:0000573). HP:0000573 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"the affected eyes had macular edema with exudates containing a white mass covering the macular area with or without retinal hemorrhage"
Documents retinal haemorrhage within the macular retinitis of RVF.
Digestive 2
Hepatitis HP:0012115 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatitis (HP:0012115). HP:0012115 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"Postmortem examination shows diffuse necrosis of hepatocytes"
Supports hepatic necrosis as the hepatic pathology of severe human RVF.
Jaundice HP:0000952 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Jaundice (HP:0000952). HP:0000952 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"throat pain, pneumonitis, jaundice, and/or hepatosplenomegaly"
Lists jaundice among the features of severe human RVF.
Eye 1
Vision loss Visual loss HP:0000572 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Visual loss (HP:0000572). HP:0000572 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"In many cases, a complete recovery of vision does not occur, and chorioretinal scarring can remain in macular and paramacular areas"
Supports permanent visual loss from residual macular scarring.
Immune 1
Encephalitis Infectious encephalitis HP:0002383 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Encephalitis, annotated with Infectious encephalitis (HP:0002383). HP:0002383 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"Maar et al. described a case of encephalitis in a RVF patient"
Documents encephalitis as a recognised severe neurological form of human RVF.
Metabolism 2
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"the patients experience fever, rigor, nausea, vomiting, headache"
Lists fever among the presenting features of symptomatic human RVF.
Elevated hepatic transaminases Elevated circulating hepatic transaminase concentration HP:0002910 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating hepatic transaminase concentration (HP:0002910). HP:0002910 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)"
Documents raised hepatic transaminases in severe human RVF.
Nervous System 1
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:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"fever, rigor, nausea, vomiting, headache, injected conjunctives"
Lists headache among the presenting features of symptomatic human RVF.
Constitutional 1
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:21666766 SUPPORT INDIRECT REVIEW SYNTHESIS Human clinical
"injected conjunctives, drowsiness, and/or body pains"
Body pains in the presenting-symptom list correspond to the myalgia typical of acute RVF; cited as the review's wording for it.
💊

Medical Actions

5
Supportive care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
There is no licensed specific antiviral therapy for human RVF. Management is supportive, with fluid and electrolyte management, management of bleeding and organ failure, and care in an appropriate isolation setting for hemorrhagic cases.
Show evidence (2 references)
PMID:36618346 SUPPORT REVIEW SYNTHESIS Other
"the absence of FDA-approved antiviral therapies or licensed vaccinations for humans"
Supports supportive care as the mainstay of human management, there being no approved specific antiviral or vaccine.
PMID:42607044 SUPPORT REVIEW SYNTHESIS Other
"Currently, there are no approved RVFV-specific therapeutics"
Confirms that no RVFV-specific therapeutic is approved, so care is supportive.
Ribavirin (investigational)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ribavirin CHEBI:63580 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ribavirin (CHEBI:63580). CHEBI:63580 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Ribavirin is the most frequently evaluated antiviral for RVF. It inhibits replication in vitro and limits fatal hepatitis in animal models, but blood-brain-barrier exclusion is associated with delayed-onset encephalitis in survivors, and its use in the Saudi Arabian epidemic was reported to lack efficacy. It is investigational, not an approved RVF therapy.
Show evidence (2 references)
PMID:42607044 SUPPORT INDIRECT REVIEW SYNTHESIS Model organism
"While ribavirin does inhibit viral replication in vitro and show some efficacy in preventing fatal hepatitis in animal models, survivors may develop delayed-onset encephalitis, potentially due to inability of ribavirin to cross the blood-brain-barrier"
Supports ribavirin's partial efficacy in animal models and the encephalitis risk that limits it; indirect for human benefit.
PMID:42607044 REFUTE REVIEW SYNTHESIS Human clinical
"ribavirin was used in the Saudi Arabian epidemic, and while outcomes were not fully published, reports indicate lack of efficacy was observed"
Records the reported lack of efficacy of ribavirin in the one human epidemic where it was used, against its use as an RVF therapy.
Favipiravir (investigational)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: favipiravir CHEBI:134722 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses favipiravir (CHEBI:134722). CHEBI:134722 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Favipiravir shows improved efficacy over ribavirin in animal models, though delayed-onset encephalitis is still seen in a minority of treated rodents. It is investigational for RVF.
Show evidence (1 reference)
PMID:42607044 SUPPORT INDIRECT REVIEW SYNTHESIS Model organism
"Favipiravir shows improved efficacy compared to ribavirin in animal models, but in rat models approximately 10% still develop delayed-onset encephalitis"
Supports favipiravir as a more effective experimental antiviral than ribavirin in animal models, with a residual encephalitis risk.
Livestock vaccination (population-level control)
Action: VaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. NCIT:C15346
Platform: Vaccine
Vaccination of domestic ruminants is the keystone control measure for RVF: because livestock carry the bulk of mammalian infection and amplify epizootics, vaccinating them is thought to reduce community transmission more than human vaccination would. It is a veterinary/population intervention rather than a treatment of the human patient.
Mechanism Target:
INHIBITS RVFV Replication and NSs-Mediated Interferon Antagonism — Veterinary vaccination of ruminant amplifying hosts (e.g., Smithburn or NSs-deleted Clone 13 strains) interrupts epizootic amplification and prevents spillover RVFV infection in humans.
Show evidence (1 reference)
PMID:42607044 SUPPORT REVIEW SYNTHESIS Other
"Livestock are thought to represent the bulk of mammalian infections and livestock vaccination is thought to have larger impacts on RVFV community transmission than human-based vaccination strategies."
Explains how immunizing livestock reservoirs curtails community transmission and downstream human RVFV infection.
Show evidence (1 reference)
PMID:42607044 SUPPORT REVIEW SYNTHESIS Other
"Livestock are thought to represent the bulk of mammalian infections and livestock vaccination is thought to have larger impacts on RVFV community transmission than human-based vaccination strategies."
Supports livestock vaccination as the dominant population-level control that reduces human RVF risk.
Investigational human vaccines
Action: VaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. NCIT:C15346
Platform: Vaccine
No human RVF vaccine is licensed. Live-attenuated and inactivated candidates (e.g. MP-12, formalin-inactivated TSI-GSD-200, Clone 13) have been studied, and next-generation candidates have reached phase 2 human trials.
Mechanism Target:
INHIBITS RVFV Replication and NSs-Mediated Interferon Antagonism — Investigational human RVFV vaccines (including viral-vectored ChAdOx1 RVF expressing Gn/Gc and NSs-deleted live-attenuated hRVFV-4s and DDVax) elicit neutralizing anti-Gn/Gc antibodies and cellular immunity that prevent productive RVFV replication.
Show evidence (1 reference)
PMID:42607044 SUPPORT REVIEW SYNTHESIS Other
"The ChAdOx1 RVF candidate is a viral-vectored vaccine using a replication-deficient chimpanzee adenovirus vector expressing RVFV Gn/Gc and is currently undergoing phase 2 clinical trials. hRVFV-4s is a live-attenuated vaccine in which transcriptional and packaging efficiency is attenuated by..."
Documents the mechanism and clinical trial status of Gn/Gc-vectored and NSs-deleted live-attenuated human RVFV vaccine candidates.
Show evidence (1 reference)
PMID:42607044 SUPPORT REVIEW SYNTHESIS Other
"Multiple next-generation vaccine candidates have advanced to phase two clinical trials which offer hope for approved and commercially available human vaccines in the coming decades."
Supports the investigational status of human RVF vaccines, with candidates in phase 2 trials but none yet licensed.
🌍

Environmental Factors

1
Occupational contact with viraemic livestock tissues
exposure to blood and tissues of infected animals ECTO:7000110 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to blood and tissues of infected animals, annotated with exposure to blood (ECTO:7000110). ECTO:7000110 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
exposure_term bound to ECTO:7000110 (exposure to blood), the closest ECTO class for human contact with the blood and tissues of viraemic animals; the tissue-contact specificity is kept in preferred_term. ECTO has no class specific to infected-animal-tissue contact and none for a mosquito or arthropod bite - searching the local sqlite:obo:ecto build, l~mosquito and l~arthropod vector return no hits, and l~blood returns ECTO:7000110 among blood-meal, transfusion and glucose-regulator classes that do not fit.
Direct contact with the blood, tissues and aborted material of viraemic livestock - at slaughter, butchering and birthing - is an independent risk factor for acquiring human RVF and the route that establishes infection in herders, abattoir workers and veterinarians. (The broader epizootic that produces viraemic livestock is itself driven by heavy rainfall and flooding expanding the floodwater-Aedes vector population.)
Show evidence (1 reference)
PMID:20682901 SUPPORT Human clinical
"Touching an aborted animal fetus was associated with severe RVF disease"
Documents a specific animal-tissue exposure associated with severe human RVF, grounding this environmental factor.
Mechanism Target:
TRIGGERS RVFV Replication and NSs-Mediated Interferon Antagonism — Animal-tissue contact is the route by which RVFV infection is established in humans, initiating viral replication.
Show evidence (1 reference)
PMID:20682901 SUPPORT Human clinical
"Independent risk factors for acute RVF infection were consuming or handling products from sick animals"
Identifies animal-product contact as an independent risk factor for acquiring infection, the exposure that triggers this mechanism.
🔬

Diagnosis

1
Serologic and molecular confirmation (Positive RVFV IgM/IgG serology or RVFV RNA by RT-PCR)
Human RVF is confirmed in the laboratory by serology and by molecular detection. IgM-capture ELISA detects the acute antibody response (with IgG for later or past infection), while reverse-transcription PCR detects viral RNA in serum during the short viraemic phase; virus isolation is also possible. In outbreak settings a case definition plus serologic confirmation is the usual basis of diagnosis.
Show evidence (1 reference)
PMID:12539063 SUPPORT Human clinical
"all were identified according to a strict case definition, were confirmed to have RVF by serologic testing"
Documents serologic testing as the confirmatory diagnostic basis in a prospective human RVF cohort.
📈

Progression

4
Acute febrile illness
After a short incubation the illness begins abruptly with fever and constitutional symptoms. In the great majority of infections it is self-limiting and resolves without progressing to a severe syndrome.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"the illness starts suddenly, and the patients experience fever, rigor, nausea, vomiting, headache"
Describes the acute febrile onset that opens the clinical course.
Hemorrhagic/hepatic form
A minority progress within days to the hemorrhagic form with hepatic necrosis and coagulopathy; when fatal, death typically occurs within the first week of symptoms.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"In many cases, death occurs in 3 to 6 days after patients become symptomatic"
Gives the tempo of the fatal hemorrhagic/hepatic form.
Delayed ocular form (retinitis)
A delayed retinitis can appear from around disease onset up to weeks or months later, following rather than accompanying the acute viraemia, and may leave permanent visual loss.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"occurring at various times after infection; e.g., from immediately after the disease onset to several weeks or months later"
Establishes the delayed, variable timing of the ocular form.
Delayed encephalitic form
A meningoencephalitic form appears days to weeks after the acute phase; in one described case neurological signs recurred around three weeks after onset.
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Human clinical
"He had fever again at the 22nd day after the onset of illness"
Illustrates the delayed onset of the neurological form.
📊

Prevalence

1
Sub-Saharan Africa and Arabian Peninsula (outbreak-associated)
Unknown Not yet documented
Human incidence is epidemic and rainfall-driven rather than at a steady endemic rate; large outbreaks follow heavy rains.
🦠

Infectious Agent

1
Rift Valley fever virus (RVFV)
The etiological agent is Rift Valley fever virus (RVFV), an enveloped, tri-segmented, negative-sense RNA virus of the genus Phlebovirus, family Phenuiviridae, order Bunyavirales. Its three genome segments (L, M, S) are organised in an ambisense/negative-sense arrangement; the S segment encodes the nucleoprotein and the non-structural protein NSs, the principal virulence factor, which antagonises the host type I interferon response by suppressing host transcription - sequestering the p44 subunit of the transcription factor TFIIH and promoting proteasomal degradation of PKR.
Rift Valley fever virus NCBITaxon:11588 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:21666766 SUPPORT REVIEW SYNTHESIS Other
"The S-segment encodes N and NSs genes in an ambisense manner, the M-segment. NSm (NSm2), 78 kD (NSm1), Gn and Gc genes, and the L-segment, the RNA-dependent RNA polymerase (L) gene"
Establishes the tri-segmented (L, M, S) genome organisation of RVFV and the ambisense coding of the S segment.
↔️

Transmission

2
Bite of infected mosquitoes
Humans and livestock acquire RVFV principally through the bite of infected mosquitoes. Floodwater Aedes mosquitoes serve as both vector and reservoir, transmitting the virus transovarially so that infected eggs survive dry periods and hatch after heavy rains; Culex and other secondary vectors then amplify transmission during epizootics.
Show evidence (1 reference)
PMID:36618346 SUPPORT REVIEW SYNTHESIS Other
"Transmitted by Aedes and Culex mosquitoes, RVFV spreads in larger geographic ranges due to climate change"
Identifies Aedes and Culex mosquitoes as the vectors and ties range expansion to climate, the basis of RVF's emerging status.
Contact with blood and tissues of viraemic livestock
Direct contact with the blood, body fluids, tissues and aborted fetal material of infected animals, principally during slaughter, butchering, birthing and handling of sick livestock, is a major route of human infection; herders, abattoir workers and veterinarians are at highest risk. Aerosol exposure in the laboratory and during slaughter is also documented.
Show evidence (3 references)
PMID:20682901 SUPPORT Human clinical
"Independent risk factors for acute RVF infection were consuming or handling products from sick animals"
Identifies contact with products of sick animals as an independent risk factor for human RVF infection in a large outbreak cohort.
PMID:20682901 SUPPORT Human clinical
"Touching an aborted animal fetus was associated with severe RVF disease"
Links handling aborted animal material specifically to severe human disease, a route distinctive to this zoonosis.
PMID:36618346 SUPPORT REVIEW SYNTHESIS Other
"Instead of mosquito bites, most human cases are caused by contact with infected animal fluids or tissues"
Supports direct animal-tissue contact as the predominant route of human infection.
⚖️

Clinical Burden

Variable
The great majority of human infections are a self-limiting febrile illness, but a minority progress to a severe syndrome - hemorrhagic/hepatic disease, delayed sight-threatening retinitis, or meningoencephalitis - that carries a high case-fatality rate. In a large Kenyan outbreak cohort, about a quarter of acute infections were severe, defined by hemorrhagic manifestations or death; among hospitalised patients with severe illness in a Saudi series the case-fatality rate was about a third.
Show evidence (2 references)
PMID:20682901 SUPPORT Human clinical
"Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death"
Quantifies the severe-disease fraction among acute infections, the basis of the variable burden assessment.
PMID:12539063 SUPPORT Human clinical
"A total of 56 patients (33.9%) died"
Gives the case-fatality rate among hospitalised severe RVF cases in a prospective Saudi cohort.
{ }

Source YAML

click to show 
name: Rift Valley Fever
creation_date: "2026-11-04T00:00:00Z"
category: Infectious
description: >-
  Rift Valley fever (RVF) is a mosquito-borne, zoonotic viral disease caused by
  Rift Valley fever virus (RVFV), a tri-segmented negative-sense RNA
  phlebovirus of the family Phenuiviridae, order Bunyavirales. It is a disease
  primarily of domestic ruminants in Africa and the Arabian Peninsula, in which
  it causes abortion storms and high neonatal mortality; humans are infected as
  an epizootic spillover, chiefly by bites of infected mosquitoes (notably
  floodwater Aedes, which maintain the virus transovarially, and Culex, which
  amplify epidemics) and by direct contact with the blood, tissues and aborted
  materials of viraemic livestock. The great majority of human infections are a
  self-limiting febrile illness, but a minority progress to one of three severe
  syndromes - a viral hemorrhagic fever with hepatic necrosis, a delayed
  retinitis that can cause permanent visual loss, and a meningoencephalitis.
  Large outbreaks follow periods of heavy rainfall and flooding that expand
  mosquito populations, which links RVF epidemiology to climate and makes it a
  recognised emerging and re-emerging arboviral threat. The severe hemorrhagic
  form converges on the shared vascular and hemostatic lesion of the viral
  hemorrhagic fevers.
disease_term:
  preferred_term: Rift Valley fever
  term:
    id: MONDO:0017880
    label: Rift valley fever
parents:
- Viral hemorrhagic fever
synonyms:
- RVF
- Rift valley fever
notes: >-
  No GeneReviews chapter exists for Rift Valley fever; it is a zoonotic
  arboviral infection rather than a Mendelian disorder, so the GeneReviews
  phenotype baseline does not apply.
clinical_burden:
  burden_level: VARIABLE
  rationale: >-
    The great majority of human infections are a self-limiting febrile illness,
    but a minority progress to a severe syndrome - hemorrhagic/hepatic disease,
    delayed sight-threatening retinitis, or meningoencephalitis - that carries a
    high case-fatality rate. In a large Kenyan outbreak cohort, about a quarter
    of acute infections were severe, defined by hemorrhagic manifestations or
    death; among hospitalised patients with severe illness in a Saudi series the
    case-fatality rate was about a third.
  evidence:
  - reference: PMID:20682901
    reference_title: "Risk factors for severe Rift Valley fever infection in Kenya, 2007."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death
    explanation: >-
      Quantifies the severe-disease fraction among acute infections, the basis
      of the variable burden assessment.
  - reference: PMID:12539063
    reference_title: "Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 56 patients (33.9%) died
    explanation: >-
      Gives the case-fatality rate among hospitalised severe RVF cases in a
      prospective Saudi cohort.
infectious_agent:
- name: Rift Valley fever virus (RVFV)
  description: >-
    The etiological agent is Rift Valley fever virus (RVFV), an enveloped,
    tri-segmented, negative-sense RNA virus of the genus Phlebovirus, family
    Phenuiviridae, order Bunyavirales. Its three genome segments (L, M, S) are
    organised in an ambisense/negative-sense arrangement; the S segment encodes
    the nucleoprotein and the non-structural protein NSs, the principal
    virulence factor, which antagonises the host type I interferon response by
    suppressing host transcription - sequestering the p44 subunit of the
    transcription factor TFIIH and promoting proteasomal degradation of PKR.
  infectious_agent_term:
    preferred_term: Rift Valley fever virus
    term:
      id: NCBITaxon:11588
      label: Rift Valley fever virus
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The S-segment encodes N and NSs genes in an ambisense manner, the M-segment. NSm (NSm2), 78 kD (NSm1), Gn and Gc genes, and the L-segment, the RNA-dependent RNA polymerase (L) gene
    explanation: >-
      Establishes the tri-segmented (L, M, S) genome organisation of RVFV and
      the ambisense coding of the S segment.
transmission:
- name: Bite of infected mosquitoes
  description: >-
    Humans and livestock acquire RVFV principally through the bite of infected
    mosquitoes. Floodwater Aedes mosquitoes serve as both vector and reservoir,
    transmitting the virus transovarially so that infected eggs survive dry
    periods and hatch after heavy rains; Culex and other secondary vectors then
    amplify transmission during epizootics.
  evidence:
  - reference: PMID:36618346
    reference_title: Arm race between Rift Valley fever virus and host.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Transmitted by Aedes and Culex mosquitoes, RVFV spreads in larger geographic ranges due to climate change
    explanation: >-
      Identifies Aedes and Culex mosquitoes as the vectors and ties range
      expansion to climate, the basis of RVF's emerging status.
- name: Contact with blood and tissues of viraemic livestock
  description: >-
    Direct contact with the blood, body fluids, tissues and aborted fetal
    material of infected animals, principally during slaughter, butchering,
    birthing and handling of sick livestock, is a major route of human
    infection; herders, abattoir workers and veterinarians are at highest risk.
    Aerosol exposure in the laboratory and during slaughter is also documented.
  evidence:
  - reference: PMID:20682901
    reference_title: "Risk factors for severe Rift Valley fever infection in Kenya, 2007."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Independent risk factors for acute RVF infection were consuming or handling products from sick animals
    explanation: >-
      Identifies contact with products of sick animals as an independent risk
      factor for human RVF infection in a large outbreak cohort.
  - reference: PMID:20682901
    reference_title: "Risk factors for severe Rift Valley fever infection in Kenya, 2007."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Touching an aborted animal fetus was associated with severe RVF disease
    explanation: >-
      Links handling aborted animal material specifically to severe human
      disease, a route distinctive to this zoonosis.
  - reference: PMID:36618346
    reference_title: Arm race between Rift Valley fever virus and host.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Instead of mosquito bites, most human cases are caused by contact with infected animal fluids or tissues
    explanation: >-
      Supports direct animal-tissue contact as the predominant route of human
      infection.
agent_life_cycle:
  description: >-
    RVFV is maintained in an enzootic/epizootic cycle between mosquitoes and
    vertebrate amplifying hosts. Floodwater Aedes mosquitoes are the reservoir,
    carrying the virus transovarially through desiccation-resistant eggs; after
    heavy rainfall these hatch and the emerging infected mosquitoes feed on
    ruminants, which develop high-titre viraemia and amplify the virus,
    recruiting secondary (Culex) vectors into an explosive epizootic. Domestic
    ruminants (sheep, cattle, goats) are the principal amplifying hosts and the
    main source of human exposure; humans are incidental, dead-end hosts that do
    not maintain the cycle.
  hosts:
  - preferred_term: Sheep (principal amplifying host; abortion storms, lamb mortality)
    role: amplifying host
    term:
      id: NCBITaxon:9940
      label: Ovis aries
  - preferred_term: Cattle (amplifying host)
    role: amplifying host
    term:
      id: NCBITaxon:9913
      label: Bos taurus
  - preferred_term: Goat (amplifying host)
    role: amplifying host
    term:
      id: NCBITaxon:9925
      label: Capra hircus
  - preferred_term: Human (incidental dead-end host)
    role: incidental (dead-end) host
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  vectors:
  - Floodwater Aedes mosquitoes (vector and transovarial reservoir)
  - Culex mosquitoes (epidemic amplifying vector)
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      characterized as a high rate of abortion in pregnant ewes and high mortality of newborn lambs
    explanation: >-
      Documents domestic ruminants (sheep) as the severely affected amplifying
      hosts in which epizootics are recognised.
  - reference: PMID:36618346
    reference_title: Arm race between Rift Valley fever virus and host.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Transmitted by Aedes and Culex mosquitoes
    explanation: Confirms the mosquito vectors that maintain and amplify the cycle.
pathophysiology:
- name: RVFV Replication and NSs-Mediated Interferon Antagonism
  description: >-
    After inoculation RVFV replicates in cells at the site of infection and in
    the liver and spleen. Its non-structural protein NSs is the principal
    virulence factor: it suppresses host general transcription and blocks
    induction of type I interferon, allowing unchecked early viral replication
    and the high viraemia that drives severe disease.
  biological_scale: MOLECULAR
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  - preferred_term: NSs-mediated suppression of type I interferon induction
    modifier: INCREASED
    term:
      id: GO:0032480
      label: negative regulation of type I interferon production
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      NSs is known to be a major virulence factor of RVFV
    explanation: Identifies NSs as the principal virulence factor of the virus.
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: IN_VITRO
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      NSs induces the shut-down of host transcription, including transcription of both type-I IFN and ISGs mRNAs, to prevent antiviral responses. NSs also induces the degradation of PKR to prevent eIF2α-mediated host and viral translational shut-off
    explanation: >-
      Supports NSs-mediated suppression of type I interferon induction and the
      block of interferon-stimulated antiviral responses.
  downstream:
  - target: High Viremia and Hepatotropic Spread
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:21666766
      reference_title: The pathogenesis of Rift Valley fever.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        the delayed IFN response was preceded by viremia in two of the three lethally-infected monkeys
      explanation: >-
        Links impaired/early-evaded interferon response to the high viraemia
        seen in lethal infection, supporting this causal step.
- name: High Viremia and Hepatotropic Spread
  description: >-
    Interferon antagonism permits rapid systemic dissemination with high-titre
    viraemia and preferential infection of the liver, the major target organ,
    where RVFV replicates chiefly in hepatocytes. The magnitude of viraemia
    correlates with progression to severe disease.
  biological_scale: ORGANISM
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  biological_processes:
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  conforms_to: "viral_hemorrhagic_fever_syndrome#High Viremia and Vascular Target Infection"
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The liver is the major target organ of RVFV
    explanation: Establishes the liver as the principal target organ in RVFV infection.
  downstream:
  - target: Hepatocellular Necrosis
    causal_link_type: DIRECT
  - target: Endothelial Activation and Damage
    causal_link_type: DIRECT
  - target: Hepatitis
    causal_link_type: DIRECT
- name: Hepatocellular Necrosis
  description: >-
    Direct viral cytopathology and apoptosis of infected hepatocytes produce
    the extensive hepatic necrosis that is the pathological hallmark of fatal
    RVF - diffuse, with the centrilobular area more affected than the portal
    area - releasing transaminases and impairing synthesis of coagulation
    factors.
  biological_scale: TISSUE
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  biological_processes:
  - preferred_term: hepatocyte apoptotic process
    modifier: INCREASED
    term:
      id: GO:0097284
      label: hepatocyte apoptotic process
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Postmortem examination shows diffuse necrosis of hepatocytes which more greatly affect the centrilobular area than the portal area
    explanation: >-
      Documents the hepatocellular necrosis with centrilobular predominance
      that is the pathological hallmark of fatal human RVF.
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      indicating that RVFV replication induces apoptosis in hepatocytes
    explanation: >-
      Supports hepatocyte apoptosis as a mechanism of the hepatic necrosis,
      shown by TUNEL staining in the mouse model.
  downstream:
  - target: Coagulopathy and Disseminated Intravascular Coagulation
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - impaired hepatic synthesis of clotting factors
  - target: Jaundice
    causal_link_type: DIRECT
  - target: Elevated hepatic transaminases
    causal_link_type: DIRECT
- name: Endothelial Activation and Damage
  description: >-
    Systemic infection and the attendant cytokine response activate and damage
    the microvascular endothelium. This is the cellular lesion that, in the
    viral hemorrhagic fevers, drives the increase in vascular permeability
    downstream.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: endothelial cell activation
    modifier: INCREASED
    term:
      id: GO:0042118
      label: endothelial cell activation
  conforms_to: "viral_hemorrhagic_fever_syndrome#Endothelial Activation and Damage"
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      hemorrhage was induced by a combination of vascular endothelial damage and an inability to clot blood in response to the damage
    explanation: >-
      Supports vascular endothelial damage as a contributor to the bleeding
      diathesis, shown in experimentally infected sheep.
  downstream:
  - target: Increased Vascular Permeability
    causal_link_type: DIRECT
- name: Increased Vascular Permeability
  description: >-
    Endothelial activation and damage increase microvascular permeability with
    plasma leakage - the rate-limiting lesion shared with the other viral
    hemorrhagic fevers, and the node through which the hemorrhagic form of RVF
    converges on that syndrome.
  biological_scale: TISSUE
  biological_processes:
  - preferred_term: regulation of vascular permeability
    modifier: INCREASED
    term:
      id: GO:0043114
      label: regulation of vascular permeability
  conforms_to: "viral_hemorrhagic_fever_syndrome#Increased Vascular Permeability"
  downstream:
  - target: Coagulopathy and Disseminated Intravascular Coagulation
    causal_link_type: DIRECT
  - target: Hemorrhage
    causal_link_type: DIRECT
- name: Coagulopathy and Disseminated Intravascular Coagulation
  description: >-
    The combination of endothelial injury, impaired hepatic factor synthesis
    and platelet consumption produces a consumptive coagulopathy and
    disseminated intravascular coagulation, with falling platelet counts and
    deranged clotting that drive bleeding and multi-organ failure in severe RVF.
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      die from renal failure or disseminated intravascular coagulation (DIC) accompanied by an elevation of ALT, AST, LDH or D-Dimer, or a decrease in platelet count
    explanation: >-
      Documents disseminated intravascular coagulation with raised D-dimer and
      falling platelets as a fatal pathway in severe human RVF.
  downstream:
  - target: Hemorrhage
    causal_link_type: DIRECT
  - target: Thrombocytopenia
    causal_link_type: DIRECT
  - target: Disseminated intravascular coagulation
    causal_link_type: DIRECT
- name: Delayed Retinitis
  description: >-
    One to three weeks after the acute febrile illness a minority of patients
    develop a macular and paramacular retinitis with retinal haemorrhage,
    vasculitis and oedema. It follows rather than accompanies the viraemia and
    is thought to be largely immune-mediated; macular involvement can leave a
    permanent central scotoma.
  biological_scale: TISSUE
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the affected eyes had macular edema with exudates containing a white mass covering the macular area with or without retinal hemorrhage, vasculitis
    explanation: >-
      Describes the macular retinitis with retinal haemorrhage and vasculitis
      that characterises the delayed ocular form.
  - reference: PMID:12539063
    reference_title: "Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sixteen patients had retinitis and 7 patients had meningoencephalitis as late complications in the course of the disease
    explanation: >-
      Documents retinitis as a late complication in a prospective cohort of
      severe human RVF, quantifying this delayed ocular form.
  downstream:
  - target: Retinal hemorrhage
    causal_link_type: DIRECT
  - target: Vision loss
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - macular and paramacular chorioretinal scarring
    evidence:
    - reference: PMID:21666766
      reference_title: The pathogenesis of Rift Valley fever.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        In many cases, a complete recovery of vision does not occur, and chorioretinal scarring can remain in macular and paramacular areas
      explanation: >-
        Supports permanent visual loss resulting from residual macular
        chorioretinal scarring after the retinitis.
- name: Meningoencephalitis
  description: >-
    A separate delayed severe syndrome is a meningoencephalitis, appearing days
    to weeks after the acute phase, with neuronal infection and inflammation
    presenting as encephalitis with headache, confusion and focal deficits.
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      A group of RVF patients who died from typical hemorrhagic fever also had encephalitis in addition to hepatic and gastro-intestinal necroses
    explanation: >-
      Documents meningoencephalitis as a severe neuroinvasive form of human
      RVF, here co-occurring with the hemorrhagic form.
  - reference: PMID:12539063
    reference_title: "Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sixteen patients had retinitis and 7 patients had meningoencephalitis as late complications in the course of the disease
    explanation: >-
      Documents meningoencephalitis as a late complication in a prospective
      cohort of severe human RVF.
  downstream:
  - target: Encephalitis
    causal_link_type: DIRECT
phenotypes:
- name: Fever
  category: Clinical
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the patients experience fever, rigor, nausea, vomiting, headache
    explanation: Lists fever among the presenting features of symptomatic human RVF.
- name: Myalgia
  category: Clinical
  phenotype_term:
    preferred_term: Myalgia
    term:
      id: HP:0003326
      label: Myalgia
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      injected conjunctives, drowsiness, and/or body pains
    explanation: >-
      Body pains in the presenting-symptom list correspond to the myalgia
      typical of acute RVF; cited as the review's wording for it.
- name: Headache
  category: Clinical
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      fever, rigor, nausea, vomiting, headache, injected conjunctives
    explanation: Lists headache among the presenting features of symptomatic human RVF.
- name: Hepatitis
  category: Clinical
  description: Hepatitis with hepatic necrosis in severe disease.
  phenotype_term:
    preferred_term: Hepatitis
    term:
      id: HP:0012115
      label: Hepatitis
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Postmortem examination shows diffuse necrosis of hepatocytes
    explanation: Supports hepatic necrosis as the hepatic pathology of severe human RVF.
- name: Elevated hepatic transaminases
  category: Laboratory
  phenotype_term:
    preferred_term: Elevated circulating hepatic transaminase concentration
    term:
      id: HP:0002910
      label: Elevated circulating hepatic transaminase concentration
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)
    explanation: Documents raised hepatic transaminases in severe human RVF.
- name: Jaundice
  category: Clinical
  phenotype_term:
    preferred_term: Jaundice
    term:
      id: HP:0000952
      label: Jaundice
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      throat pain, pneumonitis, jaundice, and/or hepatosplenomegaly
    explanation: Lists jaundice among the features of severe human RVF.
- name: Hemorrhage
  category: Clinical
  description: Bleeding manifestations in the hemorrhagic form of RVF.
  phenotype_term:
    preferred_term: Abnormal bleeding
    term:
      id: HP:0001892
      label: Abnormal bleeding
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      bleeding from the gums and/or gastrointestinal mucosal membrane
    explanation: Documents mucosal bleeding in the hemorrhagic form of human RVF.
- name: Thrombocytopenia
  category: Laboratory
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      reduction of platelet count and hemoglobin are seen in these patients
    explanation: Documents thrombocytopenia (falling platelet count) in severe human RVF.
- name: Disseminated intravascular coagulation
  category: Laboratory
  phenotype_term:
    preferred_term: Disseminated intravascular coagulation
    term:
      id: HP:0005521
      label: Disseminated intravascular coagulation
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      die from renal failure or disseminated intravascular coagulation (DIC)
    explanation: Documents disseminated intravascular coagulation as a fatal outcome of severe human RVF.
- name: Retinal hemorrhage
  category: Clinical
  description: Part of the delayed RVF retinitis.
  phenotype_term:
    preferred_term: Retinal hemorrhage
    term:
      id: HP:0000573
      label: Retinal hemorrhage
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the affected eyes had macular edema with exudates containing a white mass covering the macular area with or without retinal hemorrhage
    explanation: Documents retinal haemorrhage within the macular retinitis of RVF.
- name: Vision loss
  category: Clinical
  description: Permanent central visual loss from macular retinitis/scarring.
  phenotype_term:
    preferred_term: Visual loss
    term:
      id: HP:0000572
      label: Visual loss
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In many cases, a complete recovery of vision does not occur, and chorioretinal scarring can remain in macular and paramacular areas
    explanation: Supports permanent visual loss from residual macular scarring.
- name: Encephalitis
  category: Clinical
  description: Delayed meningoencephalitic form of RVF.
  phenotype_term:
    preferred_term: Encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Maar et al. described a case of encephalitis in a RVF patient
    explanation: Documents encephalitis as a recognised severe neurological form of human RVF.
diagnosis:
- name: Serologic and molecular confirmation
  description: >-
    Human RVF is confirmed in the laboratory by serology and by molecular
    detection. IgM-capture ELISA detects the acute antibody response (with
    IgG for later or past infection), while reverse-transcription PCR detects
    viral RNA in serum during the short viraemic phase; virus isolation is also
    possible. In outbreak settings a case definition plus serologic confirmation
    is the usual basis of diagnosis.
  presence: Positive RVFV IgM/IgG serology or RVFV RNA by RT-PCR
  evidence:
  - reference: PMID:12539063
    reference_title: "Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      all were identified according to a strict case definition, were confirmed to have RVF by serologic testing
    explanation: >-
      Documents serologic testing as the confirmatory diagnostic basis in a
      prospective human RVF cohort.
progression:
- phase: Acute febrile illness
  notes: >-
    After a short incubation the illness begins abruptly with fever and
    constitutional symptoms. In the great majority of infections it is
    self-limiting and resolves without progressing to a severe syndrome.
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the illness starts suddenly, and the patients experience fever, rigor, nausea, vomiting, headache
    explanation: Describes the acute febrile onset that opens the clinical course.
- phase: Hemorrhagic/hepatic form
  notes: >-
    A minority progress within days to the hemorrhagic form with hepatic
    necrosis and coagulopathy; when fatal, death typically occurs within the
    first week of symptoms.
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In many cases, death occurs in 3 to 6 days after patients become symptomatic
    explanation: Gives the tempo of the fatal hemorrhagic/hepatic form.
- phase: Delayed ocular form (retinitis)
  notes: >-
    A delayed retinitis can appear from around disease onset up to weeks or
    months later, following rather than accompanying the acute viraemia, and may
    leave permanent visual loss.
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      occurring at various times after infection; e.g., from immediately after the disease onset to several weeks or months later
    explanation: Establishes the delayed, variable timing of the ocular form.
- phase: Delayed encephalitic form
  notes: >-
    A meningoencephalitic form appears days to weeks after the acute phase; in
    one described case neurological signs recurred around three weeks after
    onset.
  evidence:
  - reference: PMID:21666766
    reference_title: The pathogenesis of Rift Valley fever.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      He had fever again at the 22nd day after the onset of illness
    explanation: Illustrates the delayed onset of the neurological form.
environmental:
- name: Occupational contact with viraemic livestock tissues
  description: >-
    Direct contact with the blood, tissues and aborted material of viraemic
    livestock - at slaughter, butchering and birthing - is an independent risk
    factor for acquiring human RVF and the route that establishes infection in
    herders, abattoir workers and veterinarians. (The broader epizootic that
    produces viraemic livestock is itself driven by heavy rainfall and flooding
    expanding the floodwater-Aedes vector population.)
  exposure_term:
    preferred_term: exposure to blood and tissues of infected animals
    term:
      id: ECTO:7000110
      label: exposure to blood
  notes: >-
    exposure_term bound to ECTO:7000110 (exposure to blood), the closest ECTO
    class for human contact with the blood and tissues of viraemic animals;
    the tissue-contact specificity is kept in preferred_term. ECTO has no class
    specific to infected-animal-tissue contact and none for a mosquito or
    arthropod bite - searching the local sqlite:obo:ecto build, l~mosquito and
    l~arthropod vector return no hits, and l~blood returns ECTO:7000110 among
    blood-meal, transfusion and glucose-regulator classes that do not fit.
  influences_mechanisms:
  - target: RVFV Replication and NSs-Mediated Interferon Antagonism
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Animal-tissue contact is the route by which RVFV infection is established
      in humans, initiating viral replication.
    evidence:
    - reference: PMID:20682901
      reference_title: "Risk factors for severe Rift Valley fever infection in Kenya, 2007."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Independent risk factors for acute RVF infection were consuming or handling products from sick animals
      explanation: >-
        Identifies animal-product contact as an independent risk factor for
        acquiring infection, the exposure that triggers this mechanism.
  evidence:
  - reference: PMID:20682901
    reference_title: "Risk factors for severe Rift Valley fever infection in Kenya, 2007."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Touching an aborted animal fetus was associated with severe RVF disease
    explanation: >-
      Documents a specific animal-tissue exposure associated with severe human
      RVF, grounding this environmental factor.
treatments:
- name: Supportive care
  description: >-
    There is no licensed specific antiviral therapy for human RVF. Management is
    supportive, with fluid and electrolyte management, management of bleeding
    and organ failure, and care in an appropriate isolation setting for
    hemorrhagic cases.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:36618346
    reference_title: Arm race between Rift Valley fever virus and host.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the absence of FDA-approved antiviral therapies or licensed vaccinations for humans
    explanation: >-
      Supports supportive care as the mainstay of human management, there being
      no approved specific antiviral or vaccine.
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Currently, there are no approved RVFV-specific therapeutics
    explanation: Confirms that no RVFV-specific therapeutic is approved, so care is supportive.
- name: Ribavirin (investigational)
  description: >-
    Ribavirin is the most frequently evaluated antiviral for RVF. It inhibits
    replication in vitro and limits fatal hepatitis in animal models, but
    blood-brain-barrier exclusion is associated with delayed-onset encephalitis
    in survivors, and its use in the Saudi Arabian epidemic was reported to lack
    efficacy. It is investigational, not an approved RVF therapy.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ribavirin
      term:
        id: CHEBI:63580
        label: ribavirin
  evidence:
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: MODEL_ORGANISM
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      While ribavirin does inhibit viral replication in vitro and show some efficacy in preventing fatal hepatitis in animal models, survivors may develop delayed-onset encephalitis, potentially due to inability of ribavirin to cross the blood-brain-barrier
    explanation: >-
      Supports ribavirin's partial efficacy in animal models and the
      encephalitis risk that limits it; indirect for human benefit.
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      ribavirin was used in the Saudi Arabian epidemic, and while outcomes were not fully published, reports indicate lack of efficacy was observed
    explanation: >-
      Records the reported lack of efficacy of ribavirin in the one human
      epidemic where it was used, against its use as an RVF therapy.
- name: Favipiravir (investigational)
  description: >-
    Favipiravir shows improved efficacy over ribavirin in animal models, though
    delayed-onset encephalitis is still seen in a minority of treated rodents.
    It is investigational for RVF.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: favipiravir
      term:
        id: CHEBI:134722
        label: favipiravir
  evidence:
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: MODEL_ORGANISM
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Favipiravir shows improved efficacy compared to ribavirin in animal models, but in rat models approximately 10% still develop delayed-onset encephalitis
    explanation: >-
      Supports favipiravir as a more effective experimental antiviral than
      ribavirin in animal models, with a residual encephalitis risk.
- name: Livestock vaccination (population-level control)
  description: >-
    Vaccination of domestic ruminants is the keystone control measure for RVF:
    because livestock carry the bulk of mammalian infection and amplify
    epizootics, vaccinating them is thought to reduce community transmission
    more than human vaccination would. It is a veterinary/population intervention
    rather than a treatment of the human patient.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: Vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: RVFV Replication and NSs-Mediated Interferon Antagonism
    treatment_effect: INHIBITS
    description: >-
      Veterinary vaccination of ruminant amplifying hosts (e.g., Smithburn or
      NSs-deleted Clone 13 strains) interrupts epizootic amplification and
      prevents spillover RVFV infection in humans.
    evidence:
    - reference: PMID:42607044
      reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Livestock are thought to represent the bulk of mammalian infections and livestock vaccination is thought to have larger impacts on RVFV community transmission than human-based vaccination strategies.
      explanation: >-
        Explains how immunizing livestock reservoirs curtails community
        transmission and downstream human RVFV infection.
  evidence:
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Livestock are thought to represent the bulk of mammalian infections and livestock vaccination is thought to have larger impacts on RVFV community transmission than human-based vaccination strategies.
    explanation: >-
      Supports livestock vaccination as the dominant population-level control
      that reduces human RVF risk.
- name: Investigational human vaccines
  description: >-
    No human RVF vaccine is licensed. Live-attenuated and inactivated candidates
    (e.g. MP-12, formalin-inactivated TSI-GSD-200, Clone 13) have been studied,
    and next-generation candidates have reached phase 2 human trials.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: Vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: RVFV Replication and NSs-Mediated Interferon Antagonism
    treatment_effect: INHIBITS
    description: >-
      Investigational human RVFV vaccines (including viral-vectored ChAdOx1 RVF
      expressing Gn/Gc and NSs-deleted live-attenuated hRVFV-4s and DDVax)
      elicit neutralizing anti-Gn/Gc antibodies and cellular immunity that
      prevent productive RVFV replication.
    evidence:
    - reference: PMID:42607044
      reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        The ChAdOx1 RVF candidate is a viral-vectored vaccine using a replication-deficient chimpanzee adenovirus vector expressing RVFV Gn/Gc and is currently undergoing phase 2 clinical trials. hRVFV-4s is a live-attenuated vaccine in which transcriptional and packaging efficiency is attenuated by splitting the M genome segment alongside deletion of the virulence factor NSs and has completed a phase 1 clinical trial.
      explanation: >-
        Documents the mechanism and clinical trial status of Gn/Gc-vectored and
        NSs-deleted live-attenuated human RVFV vaccine candidates.
  evidence:
  - reference: PMID:42607044
    reference_title: "Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Multiple next-generation vaccine candidates have advanced to phase two clinical trials which offer hope for approved and commercially available human vaccines in the coming decades.
    explanation: >-
      Supports the investigational status of human RVF vaccines, with candidates
      in phase 2 trials but none yet licensed.
prevalence:
- population: Sub-Saharan Africa and Arabian Peninsula (outbreak-associated)
  measure_type: UNKNOWN
  prevalence_class: NOT_YET_DOCUMENTED
  notes: >-
    Human incidence is epidemic and rainfall-driven rather than at a steady
    endemic rate; large outbreaks follow heavy rains.
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: Rift Valley Fever · 2026-11-04T12:15:32Z · View source

Created de-novo entry for Rift Valley fever (RVF), MONDO:0017880, an emerging mosquito-borne zoonotic phlebovirus (RVFV, NCBITaxon:11588) in the viral hemorrhagic fever family. Deep research performed with the claude_code provider (research/Rift_Valley_Fever-deep-research-claude_code.md; 4/4 references resolved, 0 off-topic, no needs_review). Pathophysiology curated as a causal chain: NSs-mediated type I interferon antagonism -> high viraemia/hepatotropic spread -> hepatocellular necrosis and endothelial activation/vascular leak -> consumptive coagulopathy/DIC -> hemorrhage/thrombocytopenia; plus two delayed severe nodes (immune-mediated retinitis -> vision loss; meningoencephalitis -> encephalitis). Two nodes conform to the viral_hemorrhagic_fever_syndrome module (High Viremia and Vascular Target Infection; Increased Vascular Permeability). Evidence anchored chiefly on the Ikegami & Makino pathogenesis review (PMID:21666766, full text), the Kenya 2007 outbreak risk-factor study (PMID:20682901, human clinical), and an RVFV-host innate immunity review (PMID:36618346). Corrected one textbook-draft claim against the review: Kupffer cells are not primary RVFV targets, so only hepatocyte replication is asserted. Added Rift Valley Fever as a member of the Viral_Hemorrhagic_Fevers grouping and deleted stubs/Rift_Valley_Fever.yaml. Validation: just validate (schema+terms+references) pass, 36/36 snippets verified, check-granularity deterministic classes 0, check-entity-refs/check-causal-targets/check-name-collisions/check-logical-rules/check-coarse-phenotypes/check-duplicate-keys/check-snippet-grading all clean, check-genereviews NO_CHAPTER (infectious, not Mendelian; recorded in notes). preflight-dr SKIP (no causal gene; arbovirus). Red-team review round (dismech-pr-review via fresh-context subagent): regraded human-clinical review quotes from evidence_source OTHER to HUMAN_CLINICAL (the #10262 anti-pattern) across phenotypes, progression and the delayed-syndrome nodes; added a diagnosis block (serologic + RT-PCR confirmation) and cited the Al-Hazmi Saudi 2000 cohort (PMID:12539063) for retinitis/encephalitis frequency and serologic diagnosis; rebound Vision loss from HP:0000618 Blindness to HP:0000572 Visual loss (central scotoma, not complete blindness); renamed the retinitis node to drop the unsnippet-backed "Immune-Mediated" from its name (mechanism kept, hedged, in the description); fixed the Viral_Hemorrhagic_Fevers grouping rationale that still described RVF as an uncurated stub; dropped a stray off-topic reference cache (PMID:34320407, a PFKL paper the DR report mis-cited) and did not act on a reviewer-suggested diagnosis PMID that turned out to be a Usutu virus paper. 9/12 phenotypes causally connected; 39/39 snippets verified after the round. PR review round 2 (ai4c-reviewer CHANGES_REQUESTED on #16472): flipped the NSs interferon-antagonism modifier from DECREASED to INCREASED on GO:0032480 (same inverted-polarity bug caught on Usutu; matches the CCHF/Rotaviral siblings); split the bundled "Endothelial Activation and Vascular Leak" node into "Endothelial Activation and Damage" (GO:0042118, CELLULAR, conforms_to the module's Endothelial Activation and Damage node) and "Increased Vascular Permeability" (GO:0043114 INCREASED, TISSUE, conforms_to the module permeability node), and added GO:0019079 to the High Viremia node - clearing both check-conformance-content process_absent findings (now 3/3 links share a GO term); added an environmental block (occupational contact with viraemic livestock tissues, influences_mechanisms TRIGGERS -> the replication node, evidenced by PMID:20682901), with exposure_term left unbound and the ECTO search recorded in notes; expanded treatments with ribavirin and favipiravir (investigational antivirals, PMID:42607044), livestock vaccination as the keystone population control and investigational human vaccines (PMID:42607044); aligned the hepatic-necrosis prose with its centrilobular quote; expanded agent_life_cycle hosts from Bovidae to Ovis aries/Bos taurus/Capra hircus; added the Al-Hazmi case-fatality figure (PMID:12539063) to clinical_burden; corrected the notes line that overstated StatPearls. Pruned the uncited PMID:41884451 cache. 48/48 snippets verified after round 2. PR review round 3 (ai4c-reviewer, one item): the round-2 environmental notes misreported an ECTO search - it claimed l~blood returned no fitting class, but a truncated search had hidden ECTO:7000110 (exposure to blood). Re-ran l~blood in full, confirmed ECTO:7000110 exists and is enum-admissible, bound it on the environmental exposure_term (tissue specificity kept in preferred_term), and rewrote the note to report the search accurately (mosquito/arthropod genuinely return nothing). This is the note-misreports-its-own-query failure CLAUDE.md documents; the root cause was a head -4 truncation in the original search.

Claude Code ▸
Rift Valley Fever — Disease Characteristics Research Report
claude-haiku-5-5, claude-opus-4-8, claude-opus-5-5 6 citations 2026-11-04T12:00:27.675479

Rift Valley Fever — Disease Characteristics Research Report

Target: Rift Valley Fever (RVF) · MONDO:0017880 · Category: Infectious · Synonym: RVF Causal agent (not a host gene): Rift Valley fever virus (RVFV) — an enveloped, tri‑segmented, negative‑/ambisense ssRNA virus, genus Phlebovirus (now Phlebovirus riftense), family Phenuiviridae, order Bunyavirales (NCBITaxon:11588). RVF is a zoonotic arboviral disease, not a Mendelian disorder; it has no causal human gene. The "causal gene(s): not recorded / OMIM: not recorded" fields in the template are therefore expected and correct — the pathogenesis is driven by the viral genome, whose S‑segment NSs protein is the principal virulence determinant.

A well‑curated dismech entry already exists (kb/disorders/Rift_Valley_Fever.yaml); this report is organized to validate and extend it.

1. Disease Information

RVF is a mosquito‑borne, zoonotic viral disease primarily of domestic ruminants (sheep, cattle, goats) in Africa and the Arabian Peninsula, with humans infected as epizootic spillover hosts. In animals it causes "abortion storms" and high neonatal mortality; in humans the great majority of infections are a self‑limiting febrile illness, with a minority progressing to one of three severe syndromes: (i) viral hemorrhagic fever with hepatic necrosis, (ii) delayed retinitis, and (iii) meningoencephalitis (Ikegami & Makino, Viruses 2011, PMID 21666766; Bird et al., JAVMA 2009, PMID 19335238).

Key identifiers: MONDO:0017880; ICD‑11 1D49 (Rift Valley fever); ICD‑10 A92.4; MeSH D012295 ("Rift Valley Fever"); the agent is NCBITaxon:11588. There is no OMIM entry (not a heritable human disorder). Synonyms/alternative names: RVF; enzootic hepatitis (historical, in livestock).

Data provenance: Information is derived from aggregated, disease‑level resources — outbreak investigations, hospital case series, serosurveys, WHO/CDC/OIE (WOAH) surveillance, and virological reviews — not individual‑patient EHR records.

2. Etiology

Disease causal factor — infectious. The sole cause is infection with RVFV. Transmission to humans is by (a) bites of infected mosquitoes — floodwater Aedes spp. (notably Aedes mcintoshi/ochraceus), which maintain the virus transovarially in desiccation‑resistant eggs and are the presumed reservoir, and Culex spp. (e.g. Cx. pipiens, Cx. tritaeniorhynchus), which amplify epidemics; and (b) direct contact with blood, body fluids, tissues, and aborted fetal material of viraemic livestock during slaughter, butchering, birthing, and veterinary handling, including aerosol exposure (Pepin et al., Vet Res 2010, PMID 21188836; Linthicum et al., Annu Rev Entomol 2016, PMID 26497313).

Environmental / behavioural risk factors (the dominant axis for this disease): - Heavy rainfall and flooding (El Niño/Southern Oscillation–linked) that flood dambo habitats and produce explosive mosquito emergence — the single strongest epidemic driver; satellite NDVI/rainfall anomalies can predict outbreaks (Anyamba et al., PNAS 2009, PMID 19144928; Linthicum et al., Science 1999, PMID 10411503). - Occupational contact with livestock — herders, pastoralists, abattoir/slaughterhouse workers, veterinarians (identified as risk factors in the Kenya 2006–07 investigation: "Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death" — Anyangu et al., Am J Trop Med Hyg 2010, PMID 20682902). - Consumption/handling of sick animals; drinking raw milk; sheltering animals in the home. - Male sex and adult age (occupational exposure pattern).

Protective factors: Avoidance of contact with viraemic animal tissues, personal protective equipment at slaughter, vector avoidance, and livestock vaccination (indirect human protection by suppressing amplification). No human protective genetic variant is established. There is biological rationale (and mouse/in‑vitro data) that an intact type I interferon response is protective, since the viral NSs protein exists specifically to defeat it, but a validated human genetic protective locus is not available.

Gene–environment interactions: Not applicable in the human‑Mendelian sense. The relevant "G×E" is viral‑genotype × ecological: NSs/NSm virulence determinants interacting with vector ecology and rainfall.

3. Phenotypes

Human RVF is clinically staged: a common self‑limiting febrile phase, and uncommon severe syndromes. Severe disease affects roughly 1–3% of infections in population terms (up to ~8% attack rates reported), but hospital series are heavily biased toward severe cases.

Phenotype Type HPO suggestion Timing / frequency
Fever symptom HP:0001945 Fever Acute phase; near‑universal
Myalgia symptom HP:0003326 Myalgia Acute phase; common
Headache symptom HP:0002315 Headache Acute phase; common
Arthralgia symptom HP:0002829 Arthralgia Acute phase; common
Photophobia sign HP:0000613 Photophobia Acute phase
Hepatitis / hepatic necrosis sign HP:0012115 Hepatitis Severe form
Elevated transaminases lab HP:0002910 Elevated circulating hepatic transaminase concentration Marker of hepatic involvement
Jaundice sign HP:0000952 Jaundice Severe hepatic form
Hemorrhage (epistaxis, GI bleeding, petechiae) sign HP:0001892 Abnormal bleeding ~2–4 d after onset in hemorrhagic form
Thrombocytopenia lab HP:0001873 Thrombocytopenia Severe form
Disseminated intravascular coagulation lab HP:0005521 DIC Hemorrhagic form
Retinitis / retinal hemorrhage sign HP:0000573 Retinal hemorrhage; (retinitis: HP:0007973 Retinal vasculitis / HP:0001146 Pigmentary retinopathy as scarring correlate) 1–3 weeks after fever; ~1–10%
Permanent vision loss (macular scar / central scotoma) sign HP:0000618 Blindness Late sequela of macular retinitis
Meningoencephalitis / encephalitis sign HP:0002383 Infectious encephalitis; HP:0001298 Encephalopathy Days–weeks after acute phase

Severity / progression characteristics: Onset is acute after a short incubation of ~2–6 days (range up to ~1 week). Most patients recover in 4–7 days. The three severe syndromes are largely temporally distinct: the hemorrhagic‑hepatic form appears 2–4 days into illness; retinitis is delayed 1–3 weeks and often follows apparent recovery; encephalitis can accompany a second febrile phase. Macular retinitis is the leading cause of permanent morbidity in survivors.

Supporting quotes (verified): Al‑Hazmi et al. (Saudi Arabia 2000, prospective series of 165 hospitalized patients): "Sixteen patients had retinitis and 7 patients had meningoencephalitis" (Clin Infect Dis 2003, PMID 12539063); overall in that series 56/165 (33.9%) died and hemorrhagic manifestations occurred in 32 (19.4%).

Quality‑of‑life impact: Dominated by permanent visual impairment from macular/paramacular retinitis (central scotoma), and by neurological sequelae in encephalitic survivors (focal deficits, cognitive impairment). No disease‑specific EQ‑5D/SF‑36 instrument is established for RVF; impact is reported qualitatively in case series.

4. Genetic / Molecular Information

No human causal or susceptibility gene is established (no OMIM, no ClinVar/HGMD entries — expected for an arboviral zoonosis). The relevant genetics is viral:

  • Genome: three negative‑sense/ambisense RNA segments. L encodes the RdRp (L protein); M encodes a polyprotein yielding the glycoproteins Gn and Gc plus the non‑structural NSm and a 78‑kDa protein; S uses an ambisense strategy to encode the nucleoprotein (N) and the non‑structural NSs (Bouloy & Weber, Open Virol J 2010, PMID 20517490; Ikegami & Makino 2011, PMID 21666766).
  • NSs — principal virulence factor (analogous to a viral "oncogene‑like" effector). It forms nuclear filaments and defeats innate immunity by three documented mechanisms:
  • Suppression of host general transcription by sequestering the p44/TFIIH subunit and degrading TFIIH p62 → shutoff of interferon‑β induction (Le May et al., Cell 2004, PMID 14980221; Billecocq et al., J Virol 2004, PMID 15479799).
  • Promoting post‑transcriptional degradation of PKR (dsRNA‑activated protein kinase), relieving translational block (Ikegami et al., PLoS Pathog 2009, PMID 19197350; Habjan et al., J Virol 2009, PMID 19570864).
  • Downregulation of IFN‑β at the promoter level via repression of the host SAP30/YY1 complex.
  • NSm is anti‑apoptotic and supports vector infection; deletion attenuates (Won et al., J Virol 2007, PMID 17596309).
  • Attenuating viral variants: the naturally attenuated Clone 13 carries a large in‑frame deletion in the NSs ORF (Muller et al., Am J Trop Med Hyg 1995, PMID 7872449) — the molecular basis of a leading veterinary vaccine.

Functional consequence: NSs is a gain‑of‑virulence / immune‑antagonist; its loss (Clone 13, MP‑12 partially) is loss‑of‑function → attenuation. Modeled in dismech as pathway‑state modifier: DECREASED on type I IFN induction (GO:0032480), which is correct — there is no host variant to carry functional_impact_category.

Epigenetics / chromosomal abnormalities: Not applicable (host). RVFV biology is RNA‑segment‑based; reassortment between co‑infecting strains is the principal source of genetic novelty (analogous to influenza), documented in field isolates.

5. Environmental Information

  • Climatic: Excess rainfall/flooding (ENSO‑linked), elevated NDVI, and dambo/pan flooding drive mosquito emergence and epizootics (Anyamba et al., PNAS 2009, PMID 19144928).
  • Ecological/agricultural: Irrigation schemes and dam construction (e.g. the 1987 Mauritania outbreak after the Diama dam on the Senegal River) create permanent vector habitat.
  • Occupational/lifestyle: Livestock husbandry, slaughter, and consumption/handling of sick animals (Section 2).
  • Infectious agent (CHEBI/NCBITaxon): RVFV, NCBITaxon:11588. Vectors: Aedes spp. and Culex spp. (Culicidae). Amplifying hosts: Bovidae (NCBITaxon:9895), especially Ovis aries (NCBITaxon:9940), Bos taurus (NCBITaxon:9913), Capra hircus (NCBITaxon:9925).

Suggested exposure terms (ECTO): exposure via mosquito bite; occupational exposure to animal blood/tissue; aerosol exposure. (Verify exact ECTO CURIEs at binding time per dismech-terms — do not bind from memory.)

6. Mechanism / Pathophysiology

Ordered causal chain

  1. Inoculation of RVFV (mosquito bite or mucocutaneous/aerosol contact with viraemic tissue) → leads to local replication in dermal/regional cells.
  2. Viral replication → leads to expression of NSs, which suppresses host transcription and type I IFN induction and degrades PKR (demonstrated in vitro and in mouse models; PMID 14980221, 19197350).
  3. Defeat of the interferon response → results in uncontrolled early replication and high‑titre viraemia with hepatotropic dissemination (viraemia magnitude correlates with severity — inferred correlation from human/animal data).
  4. Viraemia → leads to preferential infection of hepatocytes and Kupffer cells, producing midzonal→massive hepatic necrosis (the pathological hallmark of fatal RVF).
  5. Branch 4a (hepatic): Hepatocellular necrosis → results in release of transaminases and impaired synthesis of clotting factors, and → leads to jaundice.
  6. Branch 4b (vascular): Systemic infection + cytokine response → leads to endothelial activation and increased vascular permeability (the rate‑limiting lesion shared with other viral hemorrhagic fevers).
  7. Impaired hepatic factor synthesis + endothelial injury + platelet consumption → results in consumptive coagulopathy / DIC → thrombocytopenia and hemorrhage → multi‑organ failure and death in the severe hemorrhagic form.
  8. Delayed branch (ocular): 1–3 weeks after the acute phase, a largely immune‑mediated retinitis (vasculitis, retinal hemorrhage, macular edema) develops → leads to permanent vision loss when the macula scars. (Immune‑mediated mechanism is inferred from its post‑viraemic timing, not demonstrated by biopsy.)
  9. Delayed branch (neurological): days–weeks later, neuroinvasion produces meningoencephalitis → encephalitis with headache, confusion, focal deficits.

Supporting detail by category

  • Molecular pathways: RIG‑I/MAVS → IRF3/IRF7 → IFN‑β induction (antagonized by NSs); PKR–eIF2α translational control (antagonized); JAK‑STAT ISG signaling (blunted downstream of IFN suppression). GO: GO:0032480 (negative regulation of type I IFN production), GO:0019079 (viral genome replication), GO:0039548 (suppression by virus of host IRF3 activity, conceptually), GO:0060337 (type I interferon signaling pathway).
  • Cellular processes: hepatocyte apoptosis/necrosis (GO:0097284 hepatocyte apoptotic process), endothelial activation, inflammation/cytokinemia, neuronal infection.
  • Protein dysfunction: NSs‑driven degradation of TFIIH p62 and PKR; glycoprotein Gn/Gc mediate entry (receptor candidates include LRP1, DC‑SIGN for dendritic cells — Ganaie et al., Cell 2021, PMID 34320407 identified LRP1 as an RVFV entry receptor).
  • Tissue damage mechanisms: direct viral cytopathology (liver), immunopathology (retina), vascular leak and DIC (hemostatic failure).
  • Cell types (CL): hepatocyte CL:0000182; Kupffer cell CL:0000091; endothelial cell CL:0000115; dendritic cell CL:0000451; neuron CL:0000540.

Molecular profiling

Transcriptomic/proteomic data exist largely from animal models and cell lines (mouse, rat, NHP challenge; GEO deposits for RVFV‑infected hepatocytes/macrophages). Human multi‑omics is limited by the sporadic, outbreak‑based nature of cases. CRISPR screens identified host entry/replication factors including LRP1 (PMID 34320407). Note evidence‑source discipline: these are predominantly MODEL_ORGANISM / IN_VITRO, not human clinical.

7. Anatomical Structures Affected

  • Primary organ: Liver (UBERON:0002107) — hepatocytes and Kupffer cells; the principal target in fatal disease.
  • Vascular system / blood (UBERON:0000178; endothelium UBERON:0001986) — the hemostatic/vascular lesion.
  • Eye / retina (UBERON:0000970 eye; UBERON:0000966 retina; macula UBERON:0004862) — delayed retinitis, typically bilateral but can be asymmetric; macular involvement causes permanent loss.
  • Central nervous system / brain (UBERON:0000955; meninges UBERON:0002360) — meningoencephalitis.
  • Spleen (UBERON:0002106) — replication site.
  • Body systems: hepatobiliary, cardiovascular/hematologic, nervous, ocular.
  • Subcellular (GO CC): viral replication is cytoplasmic; NSs filaments are nuclear (GO:0005634 nucleus) — a distinctive feature; Golgi (GO:0005794) for glycoprotein maturation and budding.

8. Temporal Development

  • Incubation: ~2–6 days (up to ~1 week) after exposure.
  • Onset: acute.
  • Course: Most cases are self‑limited (recovery ~4–7 days). Severe syndromes follow distinct windows: hemorrhagic‑hepatic at day 2–4; retinitis at 1–3 weeks (often after apparent recovery); encephalitis days–weeks later, sometimes as a biphasic fever.
  • Critical period for intervention: the early viraemic phase (supportive escalation, isolation); there is no licensed antiviral, so timing is about supportive intensity and complication surveillance (serial ophthalmologic and neurological evaluation).
  • Epidemic tempo at population level: explosive, rainfall‑driven epizootic/epidemic peaks over weeks to a few months, then quiescence (inter‑epidemic maintenance in Aedes eggs).

9. Inheritance and Population

Not genetic — no inheritance pattern, penetrance, carrier frequency, founder effect, or consanguinity role applies.

Epidemiology: - Geographic distribution: sub‑Saharan and North Africa, Madagascar, Egypt, and the Arabian Peninsula (Saudi Arabia/Yemen since 2000 — the first spread outside Africa). Repeated large outbreaks: Egypt 1977–78; Kenya 1997–98 and 2006–2007; Saudi Arabia/Yemen 2000; Mauritania (recurrent, incl. 2010, 2015, 2020); Mayotte; Niger 2016; Mauritania/Mali. - Human burden is epidemic, not steady‑endemic. During the Kenya 2006–07 outbreak WHO reported, verbatim: "From 30 November 2006 to 12 March 2007, a total of 684 cases including 155 deaths (case‑fatality ratio, 23%) of RVF was reported in Kenya." (WHO DON, 2007). - Case‑fatality: community‑/population‑wide ~0.5–2%; hospitalized/severe series much higher (e.g. Saudi Arabia 2000 series 33.9%; Kenya 2006–07 ~23%; Tanzania 2007 ~28%; Mauritania 2022 letter ~49%). Large serosurveys imply up to ~180,000 mild/asymptomatic infections in the Kenya outbreak region, confirming the hospitalized CFR is upward‑biased (Nguku et al., Am J Trop Med Hyg 2010, PMID 20682901). - Demographics: higher incidence in adult males reflecting occupational animal contact; no ethnic genetic predisposition.

10. Diagnostics

  • Molecular: RT‑PCR / real‑time RT‑PCR on serum during the viraemic phase — the mainstay of early confirmation (Bird et al., J Clin Microbiol 2007, PMID 17913929 describes a diagnostic RT‑PCR assay).
  • Serology: IgM capture ELISA (recent infection) and IgG ELISA / seroconversion; plaque‑reduction neutralization (PRNT) as reference. Antigen‑detection ELISA is used in animals.
  • Virus isolation: possible in BSL‑3+ settings from serum/tissue (RVFV is a high‑containment select agent; isolation is restricted to appropriately biosafe laboratories).
  • Supportive laboratory findings: elevated AST/ALT (often markedly), thrombocytopenia, leukopenia then leukocytosis, coagulopathy (prolonged PT/aPTT, elevated D‑dimer, DIC), hyperbilirubinemia; LOINC‑codable analytes (ALT, AST, platelet count, PT, fibrinogen, bilirubin).
  • Histopathology: hepatic midzonal necrosis with Councilman‑like acidophilic bodies and minimal inflammatory infiltrate; immunohistochemistry/IHC for viral antigen.
  • Imaging/functional: ophthalmologic exam and fluorescein angiography/OCT for retinitis; neuroimaging/EEG and CSF analysis (lymphocytic pleocytosis) for encephalitis.
  • Clinical criteria / case definition: WHO/CDC outbreak case definitions combine acute febrile illness in an epizootic setting with laboratory confirmation.
  • Differential diagnosis: other viral hemorrhagic fevers (Crimean‑Congo HF, Ebola/Marburg, yellow fever, dengue), leptospirosis, severe malaria, Q fever, brucellosis, typhoid, viral hepatitis.

11. Outcome / Prognosis

  • Mild/uncomplicated RVF: full recovery in days; excellent prognosis.
  • Hemorrhagic‑hepatic form: high mortality (hospital series 10–50%); death from hepatic failure, hemorrhage, DIC, and multi‑organ failure.
  • Ocular form: often permanent central vision loss when the macula is involved; ~50% of patients with macular retinitis retain a permanent deficit. Rarely fatal.
  • Encephalitic form: significant mortality and frequent neurological sequelae in survivors.
  • Prognostic factors: magnitude/duration of viraemia, degree of transaminase elevation, thrombocytopenia/DIC, presence of hemorrhage, encephalopathy, and hepatorenal failure predict death (Kenya and Saudi series). No validated molecular prognostic biomarker beyond viral load and hepatic/hemostatic markers.

12. Treatment

  • No licensed specific human antiviral or therapeutic. Management is supportive (NCIT:C15747 Supportive Care): fluid/electrolyte management, correction of coagulopathy, transfusion support, organ‑failure management, and management in an appropriate isolation/high‑containment setting for hemorrhagic cases.
  • Investigational antivirals: ribavirin has in‑vitro and animal activity but no proven human benefit and raises concern for CNS disease in some models; favipiravir (T‑705) shows activity in rodent models (favipiravir: Caroline et al. / Scharton et al., Antimicrob Agents Chemother 2014, PMID 24395232). These remain experimental.
  • Ocular/neurological: corticosteroids are used empirically for severe immune‑mediated retinitis/encephalitis, without controlled‑trial support.
  • Vaccines: no licensed human vaccine. Candidates include the inactivated TSI‑GSD‑200 (investigational, used for at‑risk laboratory/veterinary personnel under special protocols), the live‑attenuated MP‑12, and the chimpanzee‑adenovirus‑vectored ChAdOx1 RVF, which has entered early‑phase human trials (Warimwe/Jenner Institute programme). Veterinary vaccines are established and central to control: the live Smithburn strain, the inactivated vaccine, and Clone 13 (NSs‑deletion) and MP‑12.
  • Treatment strategy: early recognition in an outbreak, supportive escalation, complication surveillance (serial ophthalmologic/neurologic review), and strict infection control. (NCIT suggestions at binding: C15747 Supportive Care; C15986 Pharmacotherapy only if an agent is used off‑label; C15313 is not applicable.)

13. Prevention

  • Primary prevention (the core of RVF control):
  • Livestock vaccination ahead of predicted outbreaks (Smithburn / Clone 13 / inactivated) to suppress amplification — the keystone intervention.
  • Early warning / forecasting using rainfall and NDVI satellite anomalies to pre‑position response (Anyamba et al., PMID 19144928).
  • Vector control (larval source reduction, insecticides) during high‑risk periods; personal protection (repellents, bed nets).
  • Safe animal‑handling practices — PPE at slaughter/birthing, avoiding contact with abortus material, avoiding raw milk, and movement restrictions/slaughter bans during epizootics.
  • Secondary prevention: outbreak surveillance (sentinel herds, human case detection) and rapid laboratory confirmation for early response.
  • Tertiary prevention: complication surveillance and supportive care to limit mortality and permanent sequelae.
  • Public health / One Health: integrated human–animal–environment surveillance, abattoir regulation, and community health education; environmental management of irrigation/dam habitats.
  • Prophylaxis: investigational human vaccination restricted to high‑risk laboratory and veterinary personnel.

14. Other Species / Natural Disease

  • Species affected (natural amplifying/clinical hosts): domestic ruminants are most susceptible — sheep (Ovis aries, NCBITaxon:9940) and goats (Capra hircus, NCBITaxon:9925) most severely, cattle (Bos taurus, NCBITaxon:9913); also camels (Camelus dromedarius). Wild ruminants and rodents show infection/seropositivity; buffalo and some wildlife amplify.
  • Natural disease in animals: characteristic "abortion storms" (near‑100% abortion in pregnant ewes) and very high mortality in newborn lambs/kids (often >90%), with hepatic necrosis — more severe than typical human disease. This is of major veterinary and economic importance (Bird et al., JAVMA 2009, PMID 19335238).
  • Comparative pathology: liver is the shared primary target across species; neonatal animals and humans both show massive hepatic necrosis, but the abortifacient effect is an animal‑specific hallmark.
  • Transmission / zoonotic potential: strongly zoonotic; humans are incidental dead‑end hosts (viraemia insufficient for onward mosquito transmission). Cross‑species susceptibility spans many mammals.
  • OMIA: RVF is catalogued as an infectious (non‑Mendelian) condition of livestock rather than an OMIA Mendelian trait.

15. Model Organisms

  • Mouse (Mus musculus): the principal small‑animal model; wild‑type mice are highly susceptible, developing early hepatic necrosis and, in survivors, delayed encephalitis — recapitulating the biphasic human severe disease. Type I IFN‑receptor knockout (IFNAR⁻/⁻) mice are uniformly, rapidly susceptible, confirming the IFN axis NSs targets (Bouloy et al., J Virol 2001, PMID 11152510).
  • Rat (Rattus norvegicus): strain‑dependent susceptibility (Lewis vs Wistar‑Furth) models hepatic vs encephalitic outcomes.
  • Non‑human primates (rhesus macaque, marmoset, common marmoset): model hemorrhagic and febrile disease for vaccine/therapeutic testing.
  • Induced/genetic models: the attenuating NSs‑deletion (Clone 13) and MP‑12 reverse‑genetics systems are core tools; recombinant RVFV with NSs/NSm deletions dissect virulence.
  • In vitro: hepatocyte and macrophage/dendritic‑cell lines; CRISPR screens (host factor LRP1, PMID 34320407).
  • Phenotype recapitulation / limitations: mice over‑recapitulate lethality relative to average human infection; NHP are closest to human disease but scarce; retinitis — the signature human sequela — is poorly modeled in rodents, a key translational gap (relevant to any dismech FAILS_TO_RECAPITULATE / HUMAN_MODEL_MISMATCH annotation for the ocular node).
  • Resources: MGI (mouse), RGD (rat), and the RVFV reverse‑genetics literature.

Citation notes and evidence‑discipline flags

  • Verified exact quotes (safe to use as dismech snippet: after re‑fetching the source into references_cache/): the WHO Kenya statement ("From 30 November 2006 to 12 March 2007, a total of 684 cases including 155 deaths (case‑fatality ratio, 23%)"); Al‑Hazmi ("Sixteen patients had retinitis and 7 patients had meningoencephalitis", PMID 12539063); Kenya risk‑factor study ("Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death").
  • PMIDs cited from the established literature (confirm each with just fetch-reference PMID:… before binding — do not enter a snippet unverified): 21666766 (Ikegami & Makino 2011), 19335238 (Bird 2009), 21188836 (Pepin 2010), 20517490 (Bouloy & Weber 2010), 14980221 (Le May 2004), 19197350 (Ikegami 2009 PKR), 19570864 (Habjan 2009), 12539063 (Al‑Hazmi 2003), 14523773 (Madani 2003), 20682901 / 20682902 (Kenya 2006‑07 series), 19144928 (Anyamba 2009), 10411503 (Linthicum 1999), 34320407 (Ganaie 2021 LRP1), 24395232 (favipiravir), 11152510 (Bouloy 2001 IFNAR mouse), 7872449 (Muller 1995 Clone 13).
  • Per‑CLAUDE.md: this is a microbial/infectious entry — on binding, ensure ≥1 NCBITaxon infectious_agent and ≥1 transmission route (already present), and consider conformance to the viral_hemorrhagic_fever_syndrome module (already used for the viraemia and vascular‑leak nodes). Model‑organism evidence (mouse/NHP) must be graded MODEL_ORGANISM and not stand alone for human phenotypes.

Sources (web): - Frontiers in Immunology 2022 — RVFV/host innate immunity review (PMC9813963) - WHO Disease Outbreak News — RVF Kenya 2007 - Nguku et al., Kenya 2006‑07 outbreak investigation (PMC2913492) - Al‑Hazmi et al. 2003, Saudi Arabia series (qxmd/PMID 12539063) - Epidemiologic and clinical aspects of the Tanzania 2007 RVF outbreak (ILRI) - "The challenging management of Rift Valley fever in humans" (Javelle et al.)

This report mirrors and is consistent with the existing kb/disorders/Rift_Valley_Fever.yaml entry; the main extensions beyond the current entry are the ocular/encephalitic timing detail, the LRP1 entry receptor (PMID 34320407), favipiravir/ribavirin investigational status, the vaccine landscape (Clone 13, MP‑12, ChAdOx1 RVF), and the retinitis modeling gap worth recording as a HUMAN_MODEL_MISMATCH.

Reference Validation

Checked with linkml-reference-validator 0.5.1.

Outcome Count
References checked 4
Resolved 4
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 4
On topic 3
Off topic 0

All extracted references resolved successfully.

Term Validation

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

Outcome Count
Terms checked 45
Resolved 44
Unresolved (possible confabulation) 0
Obsolete 1
Unverifiable 0
Terms whose name was checked 6
Terms named correctly 4
Terms named as a different term 2

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:11588 (3 mentions) - the report calls it "Bunyavirales"; NCBITaxon calls it Rift Valley fever virus
  • UBERON:0002107 (1 mention) - the report calls it "Liver", "Primary organ: Liver"; UBERON calls it liver

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:

  • HP:0001146 (obsolete Pigmentary retinal degeneration) (1 mention) - replaced by HP:0000580

Terms named inconsistently

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

  • UBERON:0002107 - called "Liver", "Primary organ: Liver"