Chikungunya

Infectious Disease MONDO:0017941 Pathograph 11 Show in embeddings browser Arbovirus Infection Neglected tropical disease

Chikungunya is an arboviral disease caused by chikungunya virus and transmitted by Aedes mosquitoes, presenting with acute fever, rash, and incapacitating arthralgia.

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9
Pathophys.
4
Phenotypes
1
Hypotheses
2
Gaps
11
Pathograph
1
Medical Actions
4
Datasets
17
References
1
Deep Research
◈

Mechanistic Hypotheses

1
IL-17A signalling restrains the cardiac type I interferon response
il17a_interferon_restraint EMERGING
Evidence balance 2 support
Under this model the IL-17A that chikungunya virus infection induces in the heart is not merely a marker of inflammation but an active brake on the antiviral response: IL-17A acting through IL-17RA suppresses local type I interferon production, so viral clearance from cardiac tissue is slowed and the resulting viral burden drives myocardial inflammation and injury. The prediction that distinguishes it from a bystander account is directional and testable, and has been tested only in a preprint so far: removing IL-17A signalling should raise interferon output and lower viral burden rather than simply lowering inflammation. Genetic deletion of Il17a or Il17ra and antibody blockade of IL-17RA both do exactly that in mouse hearts and in primary human cardiac fibroblasts. The status is EMERGING rather than CANONICAL because the only source making the interferon claim is not peer reviewed, and because the peer-reviewed human data show elevated circulating IL-17 in patients without establishing its direction of effect on interferon or on the heart.
Pathograph links
IL-17RA Signalling in Cardiac Tissue -> Restrained Cardiac Type I Interferon Response DIRECT The edge that carries the emerging claim: IL-17RA signalling suppresses the local interferon response rather than merely accompanying it.
Show evidence (2 references)
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"we demonstrate that IL-17A signaling facilitates CHIKV replication via suppressing antiviral type I interferon responses"
States the hypothesis in the direction that defines this group, that IL-17A acts upstream of the interferon response rather than downstream of the damage.
PMID:35254128 SUPPORT Human Clinical
"Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease"
PARTIAL because it establishes that IL-17 is elevated in infected patients, which is the observation the hypothesis starts from, but says nothing about interferon or about the heart.
?

Discussions and Knowledge Gaps

2
Does IL-17A restrain the type I interferon response in the human chikungunya-infected heart, or is that direction of effect an artefact of an interferon-receptor-deficient mouse?
HUMAN MODEL MISMATCH OPEN hmm_il17a_cardiac_interferon_arm
Attached to
pathophysiology#Restrained Cardiac Type I Interferon Response pathophysiology#IL-17RA Signalling in Cardiac Tissue
The mismatch here is unusually pointed, because the model system is compromised in precisely the axis the hypothesis is about. The directional claim rests on a heterozygous interferon alpha, beta and gamma receptor-deficient mouse, so the interferon response being measured is already operating at reduced receptor dosage; whether the same restraint would be visible, or would matter, in a fully interferon-competent host is not established. The human arm of the same source is primary cardiac fibroblast culture, which supplies the correct species and cell type but no immune compartment, no vasculature and no chronic timescale. On the peer-reviewed side there is a clean separation of what is known: elevated IL-17 in patient sera, and IL-17A dependence of joint and muscle inflammation in mice, neither of which speaks to interferon or to the heart. Note also that the source is a preprint and has not been peer reviewed, so the usual caution about a single unreviewed result applies on top of the model question.
Proposed experiments
IL-17A blockade in an interferon-competent chikungunya cardiac model
exp_chikv_il17a_interferon_competent_host
Repeat the IL-17RA blockade and Il17a deletion experiments in an immunocompetent mouse cardiac infection model of the kind used to establish MAVS dependence, measuring cardiac interferon output and viral burden. If the interferon restraint is real rather than a consequence of reduced receptor dosage, it should be recoverable in a host with an intact receptor complement.
IL-17 and interferon signatures in human chikungunya cardiac tissue
exp_chikv_human_cardiac_il17_tissue
Measure IL-17A and type I interferon signatures in myocardial tissue or pericardial fluid from patients with chikungunya-associated cardiac disease, with arboviral and non-arboviral myocarditis comparators. The human evidence at present is serum cytokine measurement in a musculoskeletal disease cohort, which cannot localise either signal to the heart.
Show evidence (2 references)
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"Using a novel heterozygous interferon receptor-deficient mouse model"
The authors' own statement of the animal system used, which is what makes the mismatch explicit: the interferon claim is made in a host with an engineered interferon receptor deficiency.
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT In Vitro
"blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque psoriasis, Brodalumab, drastically increased type I interferon production and reduced viral replication in both human cardiac fibroblasts and human embryonic kidney 293 (HEK 293) cells"
PARTIAL, and split out from the mouse item because it is the human arm of the same study and a different evidence type: primary human cardiac fibroblast and HEK 293 culture supplies the right species and cell type but no immune compartment, vasculature or chronic timescale.
Is IL-17RA blockade a viable therapeutic strategy in chikungunya, and what would have to be shown before it could be curated as a treatment?
KNOWLEDGE GAP OPEN gap_il17ra_blockade_untested_in_human_chikungunya
Attached to
pathophysiology#IL-17RA Signalling in Cardiac Tissue
Brodalumab is an approved IL-17RA antagonist for plaque psoriasis, and the preprint reports that it raises interferon production and lowers viral replication in human cardiac fibroblasts and in HEK 293 cells, including when given after infection. That is a mechanistically coherent repurposing proposal and nothing more: there is no clinical study in chikungunya, no human safety or dosing data in acute arboviral infection, and the intervention is immunosuppressive in a setting where IL-17 also contributes to control of infection. This entry therefore deliberately carries no treatment record for IL-17RA blockade and records the proposal here instead, so that a future curator can see that the omission was a decision rather than an oversight. The bar for promoting it to a treatment with a target_mechanisms edge is a clinical study in infected patients, not a stronger preclinical result.
Proposed experiments
Controlled trial of IL-17RA blockade in acute chikungunya with cardiac involvement
exp_chikv_il17ra_blockade_clinical
A randomised controlled study of IL-17RA blockade in acute chikungunya, powered on cardiac endpoints such as troponin, echocardiographic function and arrhythmia, with viral load as a mechanistic readout and explicit monitoring for the infectious complications that IL-17 blockade is known to carry.
Show evidence (2 references)
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT In Vitro
"blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque psoriasis, Brodalumab, drastically increased type I interferon production and reduced viral replication in both human cardiac fibroblasts and human embryonic kidney 293 (HEK 293) cells"
The whole of the pharmacological evidence, and it is cell culture in human cardiac fibroblasts and a kidney cell line rather than any clinical observation.
PMID:28503297 SUPPORT Human Clinical
"Cardiac compromise is not so common in isolated episodes"
PARTIAL, and included because it bears on feasibility rather than on mechanism: the target population for a cardiac endpoint trial is a minority of infected patients, which is part of why no such study exists.
⚙

Pathophysiology

9
CHIKV Replication in Fibroblast-Lineage Target Cells
Chikungunya virus establishes productive replication preferentially in fibroblasts of muscle, joint and skin, a tropism recovered from human biopsy material as well as from the mouse model. This node is the shared root of the entry: the musculoskeletal syndrome and the cardiac arm both begin from infection of the same cell lineage in different tissues.
fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Cardiac Fibroblast Infection The same fibroblast tropism extends to the resident fibroblast population of the myocardium.
Joint and Muscle Inflammation with Neutrophil Infiltration Infection of joint and muscle fibroblasts is the substrate for the arthralgia and myalgia that define acute chikungunya.
Show evidence (1 reference)
PMID:18282093 SUPPORT Model Organism
"CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans"
Identifies the fibroblast as the predominant target cell and states that the mouse tropism matches human biopsy material, which is what licenses using this node as the root for both arms.
Cardiac Fibroblast Infection
Chikungunya virus directly infects and actively replicates in cardiac fibroblasts. This is shown in an immunocompetent mouse model and in primary human cardiac cells, so the cardiac arm rests on a demonstrated cell target rather than on the clinical association alone.
cardiac fibroblast CL:0002548 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves cardiac fibroblast, annotated with fibroblast of cardiac tissue (CL:0002548). CL:0002548 is a cell type from the Cell Ontology.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology. ↑ INCREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
IL-17A Production in Infected Heart Tissue Cardiac infection is itself the stimulus for local IL-17A production.
Show evidence (1 reference)
PMID:37537212 SUPPORT Model Organism
"we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts"
Establishes the cardiac fibroblast as a genuine replication site, using both an immunocompetent mouse model and human primary cardiac cells.
MAVS-Dependent Innate Sensing Failure
Loss of signalling through the mitochondrial antiviral-signaling protein MAVS, the adaptor for cytoplasmic viral RNA sensing. In the model system this state is produced genetically rather than by the virus, which is why it is curated as an upstream host lesion with no incoming edge from infection: the reviewer-suggested route from cardiac infection to sensing failure is not something the source shows. What the source does show is the consequence — mice deficient in MAVS signalling fail to clear chikungunya virus from the heart — so the outgoing edge, not an incoming one, is where the evidence sits. PROVISIONAL because no comparable sensing lesion has been demonstrated in patients with chikungunya cardiac disease.
cytoplasmic pattern recognition receptor signaling pathway GO:0002753 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased cytoplasmic pattern recognition receptor signaling pathway (GO:0002753). GO:0002753 is a biological process from the Gene Ontology. ↓ DECREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Restrained Cardiac Type I Interferon Response The peer-reviewed route to a cardiac interferon response too weak to clear the virus, and the counterpart of the emerging IL-17A route into the same node.
Show evidence (1 reference)
PMID:37537212 SUPPORT Model Organism
"Using mice deficient in major innate immunity signaling components, we found that signaling through the mitochondrial antiviral-signaling protein (MAVS) is required for viral clearance from the heart"
Establishes MAVS-dependent sensing as the innate signalling step whose loss prevents cardiac viral clearance, and states that the deficiency is a property of the mouse rather than an effect of the infection.
IL-17A Production in Infected Heart Tissue
IL-17A is produced locally in chikungunya-infected cardiac tissue. PROVISIONAL because the cardiac localisation rests solely on a preprint: the peer-reviewed human data measure IL-17 in patient sera and the peer-reviewed mouse data measure it in joint and muscle, so neither places the cytokine in the heart.
interleukin-17 production GO:0032620 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased interleukin-17 production (GO:0032620). GO:0032620 is a biological process from the Gene Ontology. ↑ INCREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
IL-17RA Signalling in Cardiac Tissue Locally produced IL-17A acts on cardiac cells through its receptor IL-17RA, which is the step receptor blockade interrupts.
Show evidence (2 references)
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"We found that CHIKV infection induced IL-17A production in the heart"
The only source that localises IL-17A production to cardiac tissue, and the reason this node is marked PROVISIONAL.
PMID:35254128 SUPPORT Human Clinical
"Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease"
PARTIAL because it establishes that IL-17 rises in infected patients, which is the observation this node starts from, but measures serum and so cannot place the cytokine in the heart.
IL-17RA Signalling in Cardiac Tissue
IL-17A signalling through IL-17RA in cardiac tissue. Removing the receptor or blocking it pharmacologically raises the local interferon response and lowers viral burden, so this is the step the emerging hypothesis places upstream of the interferon response rather than downstream of the damage. PROVISIONAL because every result placing IL-17RA signalling in the heart comes from the same preprint.
IL-17A signalling restrains the cardiac type I interferon response
interleukin-17-mediated signaling pathway GO:0097400 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased interleukin-17-mediated signaling pathway (GO:0097400). GO:0097400 is a biological process from the Gene Ontology. ↑ INCREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Restrained Cardiac Type I Interferon Response The edge that carries the emerging claim: IL-17RA signalling suppresses the local interferon response rather than merely accompanying it. IL-17A signalling restrains the cardiac type I interferon response
Show evidence (2 references)
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"Genetic deletion of IL-17A signaling significantly enhanced type I interferon responses and decreased viral burden in mouse hearts"
Loss of signalling through this axis changes both interferon output and viral burden in cardiac tissue, which is what makes it a node rather than a bystander observation.
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT In Vitro
"blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque psoriasis, Brodalumab, drastically increased type I interferon production and reduced viral replication in both human cardiac fibroblasts and human embryonic kidney 293 (HEK 293) cells"
Pharmacological confirmation in human cardiac fibroblasts that the receptor, specifically, carries the effect.
Restrained Cardiac Type I Interferon Response
Clearance of chikungunya virus from the heart depends on a local type I interferon response raised by both infected and uninfected cardiac cells. Anything that blunts that response therefore converts a self-limiting cardiac infection into a persistent one. Two routes to a blunted response reach this node and they differ sharply in standing: loss of MAVS-dependent innate sensing is a peer-reviewed genetic result and has its own upstream node, whereas restraint by IL-17RA signalling is the emerging claim and is marked as such on its incoming edge. The node is PROVISIONAL because interferon insufficiency has not been measured in the hearts of infected humans.
type I interferon production GO:0032606 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased type I interferon production (GO:0032606). GO:0032606 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Persistent Cardiac Viral Infection An interferon response insufficient to clear the virus leaves replicating virus in cardiac tissue.
Show evidence (2 references)
PMID:37537212 SUPPORT Model Organism
"In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells"
Establishes that the local interferon response is what normally prevents cardiac damage, which is what makes its restraint pathogenic.
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"Genetic deletion of IL-17A signaling significantly enhanced type I interferon responses and decreased viral burden in mouse hearts"
Read in reverse, intact IL-17A signalling holds the interferon response below the level the deletion reveals.
Persistent Cardiac Viral Infection
Virus that is not cleared continues to replicate in the myocardium and in the vascular tissue at the base of the heart. In the mouse this persistence is prolonged, with large vessel vasculitis still present two months after infection. Whether human cardiac involvement reflects persistence or a single acute insult has not been established, hence PROVISIONAL.
viral genome replication GO:0019079 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. ↑ INCREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Cardiac Inflammation and Myocardial Injury Persistent replication in cardiac tissue recruits the infiltrate that produces the myocardial lesion.
Show evidence (1 reference)
PMID:37537212 SUPPORT Model Organism
"Large vessel vasculitis was observed for up to 60 days post infection, suggesting CHIKV can lead to vascular inflammation and potential long-lasting cardiovascular complications"
Quantifies how long the consequences of failed clearance persist in the model, and is the authors' own hedged extrapolation to humans.
Cardiac Inflammation and Myocardial Injury
Inflammatory cell infiltration of cardiac tissue with focal myocarditis and vasculitis of the great vessels at the base of the heart. Blocking IL-17A signalling reduces the pro-inflammatory mediators, the infiltrate and the injury together, which is the observation that makes this node the endpoint of the IL-17A arm rather than an independent process.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Myocarditis The tissue lesion presenting clinically. Myocarditis is the phenotype the myocardial inflammation and injury node produces, and is named as such both in the mouse histology and in the patient literature.
Show evidence (3 references)
PMID:37537212 SUPPORT Model Organism
"In the absence of MAVS signaling, persistent infection leads to focal myocarditis and vasculitis of the large vessels attached to the base of the heart"
Names the two lesions that constitute this node in the model system.
PPR:PPR1294570 Preprint · not peer-reviewed SUPPORT Model Organism
"reduced immune cell infiltration into cardiac tissue, and mitigated cardiac injury"
Interrupting IL-17A signalling removes the infiltrate and the injury, placing this node downstream of the IL-17A arm.
PMID:28503297 SUPPORT Human Clinical
"Cardiovascular manifestations can be considered common and have been reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA"
PARTIAL because the systematic review establishes that cardiac involvement occurs in infected patients but reports no mechanism, and its own methods section notes that isolated cardiac compromise is not common.
Joint and Muscle Inflammation with Neutrophil Infiltration
Inflammatory infiltration of joint and muscle tissue, with neutrophils prominent, underlying the arthralgia and myalgia of acute chikungunya and persisting into the postacute phase. IL-17A is required for it in the mouse and is elevated in patients, most strongly during chronic disease; that dependence is recorded as evidence on this node rather than as an edge from the cardiac IL-17A nodes, because the peer-reviewed result is about joint and muscle tissue and the cardiac nodes are explicitly localised to the heart.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED neutrophil chemotaxis GO:0030593 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased neutrophil chemotaxis (GO:0030593). GO:0030593 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Arthralgia Persistent inflammation of the joint is what patients experience as the arthralgia that defines chikungunya and that outlasts the acute illness.
Show evidence (2 references)
PMID:35254128 SUPPORT Model Organism
"CHIKV-infected mice lacking IL-17A showed reduced tissue inflammation and neutrophil infiltration, compared to wild-type mice"
The genetic result defining both the composition of the infiltrate and its dependence on IL-17A.
PMID:35254128 SUPPORT Model Organism
"These investigations showed a role for IL-17 in the acute phase of CHIKV infection and also during the postacute disease resolution phase"
Extends the requirement beyond the acute phase, which matters because the human cytokine signal is strongest in chronic disease.
⬡

Pathograph

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

Phenotypes

4
Cardiovascular 1
Myocarditis HP:0012819 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myocarditis (HP:0012819). HP:0012819 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28503297 SUPPORT Human Clinical
"Cardiovascular manifestations can be considered common and have been reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA, including mainly, but no limited to: hypotension, shock and circulatory collapse, Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated..."
Systematic review of 40 reports listing myocarditis among the cardiovascular manifestations observed in patients with chikungunya.
Immune 1
Skin rash FREQUENT HP:0000988 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin rash (HP:0000988). HP:0000988 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17448935 SUPPORT
"The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
Rash is a typical feature of acute chikungunya.
Metabolism 1
Fever VERY_FREQUENT HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17448935 SUPPORT
"The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
Fever is a typical feature of acute chikungunya.
Constitutional 1
Arthralgia VERY_FREQUENT HP:0002829 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arthralgia (HP:0002829). HP:0002829 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17448935 SUPPORT
"The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
Arthralgia is a hallmark of acute chikungunya.
💊

Medical Actions

1
Symptomatic management
Action: Symptomatic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Symptomatic Therapy (NCIT:C170740). NCIT:C170740 is a clinical intervention from the NCI Thesaurus. NCIT:C170740
Supportive care for acute chikungunya.
Show evidence (1 reference)
PMID:29533749 SUPPORT
"Treatment of acute CHIK is symptomatic"
The abstract notes that acute chikungunya treatment is symptomatic.
🦠

Infectious Agent

1
Chikungunya virus
Alphavirus responsible for chikungunya disease.
Chikungunya virus NCBITaxon:37124 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:29533749 SUPPORT
"Chikungunya virus (CHIKV) is an arthropod-borne alphavirus"
The abstract identifies CHIKV as an alphavirus.
↔️

Transmission

1
Aedes mosquito transmission
Aedes aegypti and Aedes albopictus transmit chikungunya virus.
Show evidence (1 reference)
PMID:29533749 SUPPORT
"Chikungunya virus (CHIKV) is an arthropod-borne alphavirus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes."
The abstract specifies Aedes aegypti and Aedes albopictus as vectors.
📊

Related Datasets

4
Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4 geo:GSE186564
We found that Histone Deacetylase 4 is the target of human miR-122b-5p using transcriptome approach and report that HDAC4 is downregulated in CHIKV infected human macrophages through global transcriptome profiling
human BULK RNA SEQ n=18
PMID:40956096
Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Chikungunya virus persists in joint associated macrophages and promotes chronic disease [Xenium] geo:GSE300303
Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus and Ross River virus, cause long-lasting musculoskeletal pain and inflammation. However, the mechanisms driving chronic disease remain unclear. Here, we used single-cell RNA sequencing, spatial transcriptomics and flow cytometry to investigate joint-associated tissues in alphavirus-infected mice at a late stage of infection. We identified an accumulation of inflammatory macrophages in joint-associated tissues with elevated expression of inflammatory markers. These cells harbour CHIKV RNA, suggesting ongoing viral replication during chronic disease.
mouse SPATIAL TRANSCRIPTOMICS n=6
PMID:41922840
Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Chikungunya replication and infection is dependent upon and alters cellular hexosylceramide levels in Vero cells massive:MSV000096887
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes significant global mor-bidity, including fever, rash, and persistent arthralgia. Utilizing untargeted lipidomics, we investi-gated how CHIKV infection alters host cell lipid metabolism in Vero cells. CHIKV infection induced marked catabolism of hexosylceramides, reducing their levels while increasing ceramide byprod-ucts. Functional studies revealed a reliance on fatty acid synthesis, ?-oxidation, and glycosphin-golipid biosynthesis.
African green monkey METABOLOMICS
Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Chikungunya"). Retrieved 2026-08-02.
Chikungunya virus glycoprotein targeting of host factors increases viral fitness in human macrophage massive:MSV000094494
Proteomic analysis of Chikungunya virus E1 and E2 interacting proteins during macrophage infection
Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Chikungunya"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Chikungunya
creation_date: '2026-01-26T15:56:41Z'
category: Infectious Disease
description: >-
  Chikungunya is an arboviral disease caused by chikungunya virus and
  transmitted by Aedes mosquitoes, presenting with acute fever, rash,
  and incapacitating arthralgia.
disease_term:
  term:
    id: MONDO:0017941
    label: chikungunya
  preferred_term: Chikungunya
parents:
- Arbovirus Infection
- Neglected tropical disease
infectious_agent:
- name: Chikungunya virus
  infectious_agent_term:
    preferred_term: Chikungunya virus
    term:
      id: NCBITaxon:37124
      label: Chikungunya virus
  description: Alphavirus responsible for chikungunya disease.
  evidence:
  - reference: PMID:29533749
    reference_title: "Chikungunya virus: a rheumatologist's perspective."
    supports: SUPPORT
    snippet: "Chikungunya virus (CHIKV) is an arthropod-borne alphavirus"
    explanation: The abstract identifies CHIKV as an alphavirus.
agent_life_cycle:
  description: Chikungunya virus cycles between human hosts and Aedes mosquito vectors.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: definitive host
  vectors:
  - Aedes aegypti (NCBITaxon:7159)
  - Aedes albopictus (NCBITaxon:7160)
transmission:
- name: Aedes mosquito transmission
  description: Aedes aegypti and Aedes albopictus transmit chikungunya virus.
  evidence:
  - reference: PMID:29533749
    reference_title: "Chikungunya virus: a rheumatologist's perspective."
    supports: SUPPORT
    snippet: "Chikungunya virus (CHIKV) is an arthropod-borne alphavirus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes."
    explanation: The abstract specifies Aedes aegypti and Aedes albopictus as vectors.
mechanistic_hypotheses:
- hypothesis_group_id: il17a_interferon_restraint
  hypothesis_label: IL-17A signalling restrains the cardiac type I interferon response
  status: EMERGING
  description: >-
    Under this model the IL-17A that chikungunya virus infection induces in
    the heart is not merely a marker of inflammation but an active brake on
    the antiviral response: IL-17A acting through IL-17RA suppresses local
    type I interferon production, so viral clearance from cardiac tissue is
    slowed and the resulting viral burden drives myocardial inflammation and
    injury. The prediction that distinguishes it from a bystander account is
    directional and testable, and has been tested only in a preprint so far:
    removing IL-17A signalling should raise interferon output and lower viral
    burden rather than simply lowering inflammation. Genetic deletion of
    Il17a or Il17ra and antibody blockade of IL-17RA both do exactly that in
    mouse hearts and in primary human cardiac fibroblasts. The status is
    EMERGING rather than CANONICAL because the only source making the
    interferon claim is not peer reviewed, and because the peer-reviewed
    human data show elevated circulating IL-17 in patients without
    establishing its direction of effect on interferon or on the heart.
  evidence:
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: we demonstrate that IL-17A signaling facilitates CHIKV replication via
      suppressing antiviral type I interferon responses
    explanation: >-
      States the hypothesis in the direction that defines this group, that
      IL-17A acts upstream of the interferon response rather than downstream
      of the damage.
  - reference: PMID:35254128
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Sera from CHIKV-infected patients who displayed both acute and chronic
      disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially
      during the chronic phase of disease
    explanation: >-
      PARTIAL because it establishes that IL-17 is elevated in infected
      patients, which is the observation the hypothesis starts from, but says
      nothing about interferon or about the heart.
pathophysiology:
- name: CHIKV Replication in Fibroblast-Lineage Target Cells
  biological_scale: CELLULAR
  description: >-
    Chikungunya virus establishes productive replication preferentially in
    fibroblasts of muscle, joint and skin, a tropism recovered from human
    biopsy material as well as from the mouse model. This node is the shared
    root of the entry: the musculoskeletal syndrome and the cardiac arm both
    begin from infection of the same cell lineage in different tissues.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  evidence:
  - reference: PMID:18282093
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell
      and tissue tropism similar to that observed in biopsy samples of CHIKV-infected
      humans
    explanation: >-
      Identifies the fibroblast as the predominant target cell and states
      that the mouse tropism matches human biopsy material, which is what
      licenses using this node as the root for both arms.
  downstream:
  - target: Cardiac Fibroblast Infection
    causal_link_type: DIRECT
    description: >-
      The same fibroblast tropism extends to the resident fibroblast
      population of the myocardium.
  - target: Joint and Muscle Inflammation with Neutrophil Infiltration
    causal_link_type: DIRECT
    description: >-
      Infection of joint and muscle fibroblasts is the substrate for the
      arthralgia and myalgia that define acute chikungunya.
- name: Cardiac Fibroblast Infection
  biological_scale: CELLULAR
  description: >-
    Chikungunya virus directly infects and actively replicates in cardiac
    fibroblasts. This is shown in an immunocompetent mouse model and in
    primary human cardiac cells, so the cardiac arm rests on a demonstrated
    cell target rather than on the clinical association alone.
  cell_types:
  - preferred_term: cardiac fibroblast
    term:
      id: CL:0002548
      label: fibroblast of cardiac tissue
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  evidence:
  - reference: PMID:37537212
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: we demonstrate that CHIKV directly infects and actively replicates in
      cardiac fibroblasts
    explanation: >-
      Establishes the cardiac fibroblast as a genuine replication site, using
      both an immunocompetent mouse model and human primary cardiac cells.
  downstream:
  - target: IL-17A Production in Infected Heart Tissue
    causal_link_type: DIRECT
    description: >-
      Cardiac infection is itself the stimulus for local IL-17A production.
    evidence:
    - reference: PPR:PPR1294570
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: We found that CHIKV infection induced IL-17A production in the heart
      explanation: >-
        Places IL-17A downstream of cardiac infection rather than as a
        pre-existing host state.
- name: MAVS-Dependent Innate Sensing Failure
  biological_scale: MOLECULAR
  mechanism_confidence: PROVISIONAL
  description: >-
    Loss of signalling through the mitochondrial antiviral-signaling protein
    MAVS, the adaptor for cytoplasmic viral RNA sensing. In the model system
    this state is produced genetically rather than by the virus, which is why
    it is curated as an upstream host lesion with no incoming edge from
    infection: the reviewer-suggested route from cardiac infection to sensing
    failure is not something the source shows. What the source does show is
    the consequence — mice deficient in MAVS signalling fail to clear
    chikungunya virus from the heart — so the outgoing edge, not an incoming
    one, is where the evidence sits. PROVISIONAL because no comparable
    sensing lesion has been demonstrated in patients with chikungunya cardiac
    disease.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: cytoplasmic pattern recognition receptor signaling pathway
    modifier: DECREASED
    term:
      id: GO:0002753
      label: cytoplasmic pattern recognition receptor signaling pathway
  evidence:
  - reference: PMID:37537212
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: Using mice deficient in major innate immunity signaling components,
      we found that signaling through the mitochondrial antiviral-signaling protein
      (MAVS) is required for viral clearance from the heart
    explanation: >-
      Establishes MAVS-dependent sensing as the innate signalling step whose
      loss prevents cardiac viral clearance, and states that the deficiency
      is a property of the mouse rather than an effect of the infection.
  downstream:
  - target: Restrained Cardiac Type I Interferon Response
    causal_link_type: DIRECT
    description: >-
      The peer-reviewed route to a cardiac interferon response too weak to
      clear the virus, and the counterpart of the emerging IL-17A route into
      the same node.
    evidence:
    - reference: PMID:37537212
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: In the absence of MAVS signaling, persistent infection leads to focal
        myocarditis and vasculitis of the large vessels attached to the base of the
        heart
      explanation: >-
        The loss-of-function result: without MAVS signalling the interferon
        response no longer clears the virus and cardiac disease follows.
- name: IL-17A Production in Infected Heart Tissue
  biological_scale: MOLECULAR
  mechanism_confidence: PROVISIONAL
  description: >-
    IL-17A is produced locally in chikungunya-infected cardiac tissue.
    PROVISIONAL because the cardiac localisation rests solely on a preprint:
    the peer-reviewed human data measure IL-17 in patient sera and the
    peer-reviewed mouse data measure it in joint and muscle, so neither
    places the cytokine in the heart.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: interleukin-17 production
    modifier: INCREASED
    term:
      id: GO:0032620
      label: interleukin-17 production
  evidence:
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: We found that CHIKV infection induced IL-17A production in the heart
    explanation: >-
      The only source that localises IL-17A production to cardiac tissue, and
      the reason this node is marked PROVISIONAL.
  - reference: PMID:35254128
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Sera from CHIKV-infected patients who displayed both acute and chronic
      disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially
      during the chronic phase of disease
    explanation: >-
      PARTIAL because it establishes that IL-17 rises in infected patients,
      which is the observation this node starts from, but measures serum and
      so cannot place the cytokine in the heart.
  downstream:
  - target: IL-17RA Signalling in Cardiac Tissue
    causal_link_type: DIRECT
    description: >-
      Locally produced IL-17A acts on cardiac cells through its receptor
      IL-17RA, which is the step receptor blockade interrupts.
    evidence:
    - reference: PPR:PPR1294570
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque
        psoriasis, Brodalumab, drastically increased type I interferon production
        and reduced viral replication in both human cardiac fibroblasts and human
        embryonic kidney 293 (HEK 293) cells
      explanation: >-
        Blocking the receptor reverses the effect of the ligand, which is what
        types this as a ligand-to-receptor-signalling edge rather than an
        assumed one.
- name: IL-17RA Signalling in Cardiac Tissue
  biological_scale: MOLECULAR
  mechanism_confidence: PROVISIONAL
  description: >-
    IL-17A signalling through IL-17RA in cardiac tissue. Removing the
    receptor or blocking it pharmacologically raises the local interferon
    response and lowers viral burden, so this is the step the emerging
    hypothesis places upstream of the interferon response rather than
    downstream of the damage. PROVISIONAL because every result placing
    IL-17RA signalling in the heart comes from the same preprint.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: interleukin-17-mediated signaling pathway
    modifier: INCREASED
    term:
      id: GO:0097400
      label: interleukin-17-mediated signaling pathway
  evidence:
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: Genetic deletion of IL-17A signaling significantly enhanced type I interferon
      responses and decreased viral burden in mouse hearts
    explanation: >-
      Loss of signalling through this axis changes both interferon output and
      viral burden in cardiac tissue, which is what makes it a node rather
      than a bystander observation.
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque
      psoriasis, Brodalumab, drastically increased type I interferon production and
      reduced viral replication in both human cardiac fibroblasts and human embryonic
      kidney 293 (HEK 293) cells
    explanation: >-
      Pharmacological confirmation in human cardiac fibroblasts that the
      receptor, specifically, carries the effect.
  downstream:
  - target: Restrained Cardiac Type I Interferon Response
    causal_link_type: DIRECT
    hypothesis_groups:
    - il17a_interferon_restraint
    description: >-
      The edge that carries the emerging claim: IL-17RA signalling suppresses
      the local interferon response rather than merely accompanying it.
    evidence:
    - reference: PPR:PPR1294570
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Genetic deletion of IL-17A signaling significantly enhanced type I
        interferon responses and decreased viral burden in mouse hearts
      explanation: >-
        A loss-of-function result in the direction the hypothesis predicts,
        and the strongest single statement of the causal claim.
- name: Restrained Cardiac Type I Interferon Response
  biological_scale: TISSUE
  mechanism_confidence: PROVISIONAL
  description: >-
    Clearance of chikungunya virus from the heart depends on a local type I
    interferon response raised by both infected and uninfected cardiac cells.
    Anything that blunts that response therefore converts a self-limiting
    cardiac infection into a persistent one. Two routes to a blunted response
    reach this node and they differ sharply in standing: loss of
    MAVS-dependent innate sensing is a peer-reviewed genetic result and has
    its own upstream node, whereas restraint by IL-17RA signalling is the
    emerging claim and is marked as such on its incoming edge. The node is
    PROVISIONAL because interferon insufficiency has not been measured in the
    hearts of infected humans.
  biological_processes:
  - preferred_term: type I interferon production
    modifier: DECREASED
    term:
      id: GO:0032606
      label: type I interferon production
  evidence:
  - reference: PMID:37537212
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: In immunocompetent mice, CHIKV is cleared from cardiac tissue without
      significant damage through the induction of a local type I interferon response
      from both infected and non-infected cardiac cells
    explanation: >-
      Establishes that the local interferon response is what normally
      prevents cardiac damage, which is what makes its restraint pathogenic.
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: Genetic deletion of IL-17A signaling significantly enhanced type I interferon
      responses and decreased viral burden in mouse hearts
    explanation: >-
      Read in reverse, intact IL-17A signalling holds the interferon response
      below the level the deletion reveals.
  downstream:
  - target: Persistent Cardiac Viral Infection
    causal_link_type: DIRECT
    description: >-
      An interferon response insufficient to clear the virus leaves
      replicating virus in cardiac tissue.
    evidence:
    - reference: PMID:37537212
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: In the absence of MAVS signaling, persistent infection leads to focal
        myocarditis and vasculitis of the large vessels attached to the base of the
        heart
      explanation: >-
        Directly links failed innate antiviral signalling to persistence in
        the heart.
- name: Persistent Cardiac Viral Infection
  biological_scale: TISSUE
  mechanism_confidence: PROVISIONAL
  description: >-
    Virus that is not cleared continues to replicate in the myocardium and in
    the vascular tissue at the base of the heart. In the mouse this
    persistence is prolonged, with large vessel vasculitis still present two
    months after infection. Whether human cardiac involvement reflects
    persistence or a single acute insult has not been established, hence
    PROVISIONAL.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  evidence:
  - reference: PMID:37537212
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: Large vessel vasculitis was observed for up to 60 days post infection,
      suggesting CHIKV can lead to vascular inflammation and potential long-lasting
      cardiovascular complications
    explanation: >-
      Quantifies how long the consequences of failed clearance persist in the
      model, and is the authors' own hedged extrapolation to humans.
  downstream:
  - target: Cardiac Inflammation and Myocardial Injury
    causal_link_type: DIRECT
    description: >-
      Persistent replication in cardiac tissue recruits the infiltrate that
      produces the myocardial lesion.
- name: Cardiac Inflammation and Myocardial Injury
  biological_scale: TISSUE
  description: >-
    Inflammatory cell infiltration of cardiac tissue with focal myocarditis
    and vasculitis of the great vessels at the base of the heart. Blocking
    IL-17A signalling reduces the pro-inflammatory mediators, the infiltrate
    and the injury together, which is the observation that makes this node
    the endpoint of the IL-17A arm rather than an independent process.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37537212
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: In the absence of MAVS signaling, persistent infection leads to focal
      myocarditis and vasculitis of the large vessels attached to the base of the
      heart
    explanation: >-
      Names the two lesions that constitute this node in the model system.
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: reduced immune cell infiltration into cardiac tissue, and mitigated cardiac
      injury
    explanation: >-
      Interrupting IL-17A signalling removes the infiltrate and the injury,
      placing this node downstream of the IL-17A arm.
  - reference: PMID:28503297
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: 'Cardiovascular manifestations can be considered common and have been
      reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA'
    explanation: >-
      PARTIAL because the systematic review establishes that cardiac
      involvement occurs in infected patients but reports no mechanism, and
      its own methods section notes that isolated cardiac compromise is not
      common.
  downstream:
  - target: Myocarditis
    causal_link_type: DIRECT
    description: >-
      The tissue lesion presenting clinically. Myocarditis is the phenotype
      the myocardial inflammation and injury node produces, and is named as
      such both in the mouse histology and in the patient literature.
    evidence:
    - reference: PMID:28503297
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: 'Cardiovascular manifestations can be considered common and have been
        reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA,
        including mainly, but no limited to: hypotension, shock and circulatory collapse,
        Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated cardiomyopathy,
        congestive insufficiency, heart failure and altered function profile (Troponins,
        CPK).'
      explanation: >-
        Names myocarditis among the cardiovascular manifestations observed in
        infected patients, which is the clinical expression of this node.
- name: Joint and Muscle Inflammation with Neutrophil Infiltration
  biological_scale: TISSUE
  description: >-
    Inflammatory infiltration of joint and muscle tissue, with neutrophils
    prominent, underlying the arthralgia and myalgia of acute chikungunya and
    persisting into the postacute phase. IL-17A is required for it in the
    mouse and is elevated in patients, most strongly during chronic disease;
    that dependence is recorded as evidence on this node rather than as an
    edge from the cardiac IL-17A nodes, because the peer-reviewed result is
    about joint and muscle tissue and the cardiac nodes are explicitly
    localised to the heart.
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: neutrophil chemotaxis
    modifier: INCREASED
    term:
      id: GO:0030593
      label: neutrophil chemotaxis
  evidence:
  - reference: PMID:35254128
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: CHIKV-infected mice lacking IL-17A showed reduced tissue inflammation
      and neutrophil infiltration, compared to wild-type mice
    explanation: >-
      The genetic result defining both the composition of the infiltrate and
      its dependence on IL-17A.
  - reference: PMID:35254128
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: These investigations showed a role for IL-17 in the acute phase of CHIKV
      infection and also during the postacute disease resolution phase
    explanation: >-
      Extends the requirement beyond the acute phase, which matters because
      the human cytokine signal is strongest in chronic disease.
  downstream:
  - target: Arthralgia
    causal_link_type: DIRECT
    description: >-
      Persistent inflammation of the joint is what patients experience as the
      arthralgia that defines chikungunya and that outlasts the acute
      illness.
    evidence:
    - reference: PMID:35254128
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Up to 40% of patients experience persistent joint inflammation and
        arthralgia, which can persist for months or years after infection
      explanation: >-
        States joint inflammation and arthralgia together in patients, which
        is what links this tissue node to the phenotype.
phenotypes:
- name: Fever
  category: Systemic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:17448935
    reference_title: "Chikungunya, an epidemic arbovirosis."
    supports: SUPPORT
    snippet: "The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
    explanation: Fever is a typical feature of acute chikungunya.
- name: Skin rash
  category: Dermatologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Skin rash
    term:
      id: HP:0000988
      label: Skin rash
  evidence:
  - reference: PMID:17448935
    reference_title: "Chikungunya, an epidemic arbovirosis."
    supports: SUPPORT
    snippet: "The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
    explanation: Rash is a typical feature of acute chikungunya.
- name: Arthralgia
  category: Musculoskeletal
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: PMID:17448935
    reference_title: "Chikungunya, an epidemic arbovirosis."
    supports: SUPPORT
    snippet: "The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia."
    explanation: Arthralgia is a hallmark of acute chikungunya.
- name: Myocarditis
  category: Cardiovascular
  description: >-
    Myocardial inflammation reported among the cardiovascular manifestations
    of systemic chikungunya virus infection, alongside arrhythmias, dilated
    cardiomyopathy and heart failure. No frequency band is asserted: the
    source that establishes these manifestations occur also states that
    isolated cardiac compromise is uncommon, and the two statements cannot be
    reconciled into a band without going beyond what is reported.
  phenotype_term:
    preferred_term: Myocarditis
    term:
      id: HP:0012819
      label: Myocarditis
  evidence:
  - reference: PMID:28503297
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: 'Cardiovascular manifestations can be considered common and have been
      reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA,
      including mainly, but no limited to: hypotension, shock and circulatory collapse,
      Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated cardiomyopathy,
      congestive insufficiency, heart failure and altered function profile (Troponins,
      CPK).'
    explanation: >-
      Systematic review of 40 reports listing myocarditis among the
      cardiovascular manifestations observed in patients with chikungunya.
treatments:
- name: Symptomatic management
  description: Supportive care for acute chikungunya.
  treatment_term:
    preferred_term: Symptomatic Therapy
    term:
      id: NCIT:C170740
      label: Symptomatic Therapy
  evidence:
  - reference: PMID:29533749
    reference_title: "Chikungunya virus: a rheumatologist's perspective."
    supports: SUPPORT
    snippet: "Treatment of acute CHIK is symptomatic"
    explanation: The abstract notes that acute chikungunya treatment is symptomatic.
references:
- reference: DOI:10.1002/hsr2.2183
  title: 'Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: 'Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives'
    supporting_text: 'Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives'
- reference: DOI:10.1007/s40259-024-00677-y
  title: 'Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: 'Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure'
    supporting_text: 'Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure'
- reference: DOI:10.1080/22221751.2024.2362941
  title: 'Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: 'Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages'
    supporting_text: 'Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages'
- reference: DOI:10.1093/jtm/taae123
  title: 'From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries.
    supporting_text: Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries.
    evidence:
    - reference: DOI:10.1093/jtm/taae123
      reference_title: 'From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.1186/s12985-025-02721-x
  title: Long-term persistence of serum IgM antibodies against chikungunya virus in patients with chronic arthralgia
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown.
    supporting_text: Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown.
    evidence:
    - reference: DOI:10.1186/s12985-025-02721-x
      reference_title: Long-term persistence of serum IgM antibodies against chikungunya virus in patients with chronic arthralgia
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.1371/journal.pntd.0011037
  title: 'Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya-fever (CHIKF) remains a public health major issue.
    supporting_text: Chikungunya-fever (CHIKF) remains a public health major issue.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0011037
      reference_title: 'Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Chikungunya-fever (CHIKF) remains a public health major issue.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.1371/journal.pntd.0012254
  title: 'Clinical outcomes of chikungunya: A systematic literature review and meta-analysis'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya is a viral disease caused by a mosquito-borne alphavirus.
    supporting_text: Chikungunya is a viral disease caused by a mosquito-borne alphavirus.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0012254
      reference_title: 'Clinical outcomes of chikungunya: A systematic literature review and meta-analysis'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Chikungunya is a viral disease caused by a mosquito-borne alphavirus.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.1371/journal.pntd.0012904
  title: 'Chikungunya virus in Europe: A retrospective epidemiology study from 2007 to 2023'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide.
    supporting_text: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0012904
      reference_title: 'Chikungunya virus in Europe: A retrospective epidemiology study from 2007 to 2023'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3389/fitd.2024.1466207
  title: Excess mortality associated with chikungunya epidemic in Southeast Brazil, 2023
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics.
    supporting_text: The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics.
    evidence:
    - reference: DOI:10.3389/fitd.2024.1466207
      reference_title: Excess mortality associated with chikungunya epidemic in Southeast Brazil, 2023
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3390/diagnostics13132306
  title: 'Performance Evaluation of VIDAS® Diagnostic Assays Detecting Anti-Chikungunya Virus IgM and IgG Antibodies: An International Study'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika.
    supporting_text: Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika.
    evidence:
    - reference: DOI:10.3390/diagnostics13132306
      reference_title: 'Performance Evaluation of VIDAS® Diagnostic Assays Detecting Anti-Chikungunya Virus IgM and IgG Antibodies: An International Study'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3390/tropicalmed8070365
  title: 'Chikungunya Virus Diagnosis: A Review of Current Antigen Detection Methods'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV).
    supporting_text: Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV).
    evidence:
    - reference: DOI:10.3390/tropicalmed8070365
      reference_title: 'Chikungunya Virus Diagnosis: A Review of Current Antigen Detection Methods'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV).
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3390/tropicalmed9100247
  title: 'Chronic Rheumatologic Disease in Chikungunya Virus Fever: Results from a Cohort Study Conducted in Piedecuesta, Colombia'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia.
    supporting_text: This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia.
    evidence:
    - reference: DOI:10.3390/tropicalmed9100247
      reference_title: 'Chronic Rheumatologic Disease in Chikungunya Virus Fever: Results from a Cohort Study Conducted in Piedecuesta, Colombia'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3390/v18040428
  title: Pathogenesis of Chronic Arthritis Due to Chikungunya Virus and Advances in Vaccine Development
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus.
    supporting_text: Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus.
    evidence:
    - reference: DOI:10.3390/v18040428
      reference_title: Pathogenesis of Chronic Arthritis Due to Chikungunya Virus and Advances in Vaccine Development
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.3390/vaccines13060576
  title: Comprehensive Assessment of Reactogenicity and Safety of the Live-Attenuated Chikungunya Vaccine (IXCHIQ®)
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials.
    supporting_text: This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials.
    evidence:
    - reference: DOI:10.3390/vaccines13060576
      reference_title: Comprehensive Assessment of Reactogenicity and Safety of the Live-Attenuated Chikungunya Vaccine (IXCHIQ®)
      supports: SUPPORT
      evidence_source: OTHER
      snippet: This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.5501/wjv.v13.i2.89985
  title: Long chikungunya? An overview to immunopathology of persistent arthralgia
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years.
    supporting_text: Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years.
    evidence:
    - reference: DOI:10.5501/wjv.v13.i2.89985
      reference_title: Long chikungunya? An overview to immunopathology of persistent arthralgia
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years.
      explanation: Deep research cited this publication as relevant literature for Chikungunya.
- reference: DOI:10.59249/rqyj3197
  title: 'Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: 'Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review'
    supporting_text: 'Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review'
- reference: DOI:10.7189/jogh.16.04055
  title: 'Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study'
  found_in:
  - Chikungunya-deep-research-falcon.md
  findings:
  - statement: 'Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study'
    supporting_text: 'Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study'
discussions:
- discussion_id: hmm_il17a_cardiac_interferon_arm
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  prompt: >-
    Does IL-17A restrain the type I interferon response in the human
    chikungunya-infected heart, or is that direction of effect an artefact of
    an interferon-receptor-deficient mouse?
  rationale: >-
    The mismatch here is unusually pointed, because the model system is
    compromised in precisely the axis the hypothesis is about. The directional
    claim rests on a heterozygous interferon alpha, beta and gamma
    receptor-deficient mouse, so the interferon response being measured is
    already operating at reduced receptor dosage; whether the same restraint
    would be visible, or would matter, in a fully interferon-competent host is
    not established. The human arm of the same source is primary cardiac
    fibroblast culture, which supplies the correct species and cell type but
    no immune compartment, no vasculature and no chronic timescale. On the
    peer-reviewed side there is a clean separation of what is known: elevated
    IL-17 in patient sera, and IL-17A dependence of joint and muscle
    inflammation in mice, neither of which speaks to interferon or to the
    heart. Note also that the source is a preprint and has not been peer
    reviewed, so the usual caution about a single unreviewed result applies on
    top of the model question.
  attaches_to:
  - pathophysiology#Restrained Cardiac Type I Interferon Response
  - pathophysiology#IL-17RA Signalling in Cardiac Tissue
  proposed_experiments:
  - experiment_id: exp_chikv_il17a_interferon_competent_host
    name: IL-17A blockade in an interferon-competent chikungunya cardiac model
    description: >-
      Repeat the IL-17RA blockade and Il17a deletion experiments in an
      immunocompetent mouse cardiac infection model of the kind used to
      establish MAVS dependence, measuring cardiac interferon output and viral
      burden. If the interferon restraint is real rather than a consequence of
      reduced receptor dosage, it should be recoverable in a host with an
      intact receptor complement.
  - experiment_id: exp_chikv_human_cardiac_il17_tissue
    name: IL-17 and interferon signatures in human chikungunya cardiac tissue
    description: >-
      Measure IL-17A and type I interferon signatures in myocardial tissue or
      pericardial fluid from patients with chikungunya-associated cardiac
      disease, with arboviral and non-arboviral myocarditis comparators. The
      human evidence at present is serum cytokine measurement in a
      musculoskeletal disease cohort, which cannot localise either signal to
      the heart.
  evidence:
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: Using a novel heterozygous interferon receptor-deficient mouse model
    explanation: >-
      The authors' own statement of the animal system used, which is what
      makes the mismatch explicit: the interferon claim is made in a host with
      an engineered interferon receptor deficiency.
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque
      psoriasis, Brodalumab, drastically increased type I interferon production and
      reduced viral replication in both human cardiac fibroblasts and human embryonic
      kidney 293 (HEK 293) cells
    explanation: >-
      PARTIAL, and split out from the mouse item because it is the human arm
      of the same study and a different evidence type: primary human cardiac
      fibroblast and HEK 293 culture supplies the right species and cell type
      but no immune compartment, vasculature or chronic timescale.
- discussion_id: gap_il17ra_blockade_untested_in_human_chikungunya
  kind: KNOWLEDGE_GAP
  status: OPEN
  prompt: >-
    Is IL-17RA blockade a viable therapeutic strategy in chikungunya, and what
    would have to be shown before it could be curated as a treatment?
  rationale: >-
    Brodalumab is an approved IL-17RA antagonist for plaque psoriasis, and the
    preprint reports that it raises interferon production and lowers viral
    replication in human cardiac fibroblasts and in HEK 293 cells, including
    when given after infection. That is a mechanistically coherent
    repurposing proposal and nothing more: there is no clinical study in
    chikungunya, no human safety or dosing data in acute arboviral infection,
    and the intervention is immunosuppressive in a setting where IL-17 also
    contributes to control of infection. This entry therefore deliberately
    carries no treatment record for IL-17RA blockade and records the proposal
    here instead, so that a future curator can see that the omission was a
    decision rather than an oversight. The bar for promoting it to a
    treatment with a target_mechanisms edge is a clinical study in infected
    patients, not a stronger preclinical result.
  attaches_to:
  - pathophysiology#IL-17RA Signalling in Cardiac Tissue
  proposed_experiments:
  - experiment_id: exp_chikv_il17ra_blockade_clinical
    name: Controlled trial of IL-17RA blockade in acute chikungunya with cardiac
      involvement
    description: >-
      A randomised controlled study of IL-17RA blockade in acute chikungunya,
      powered on cardiac endpoints such as troponin, echocardiographic
      function and arrhythmia, with viral load as a mechanistic readout and
      explicit monitoring for the infectious complications that IL-17
      blockade is known to carry.
  evidence:
  - reference: PPR:PPR1294570
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque
      psoriasis, Brodalumab, drastically increased type I interferon production and
      reduced viral replication in both human cardiac fibroblasts and human embryonic
      kidney 293 (HEK 293) cells
    explanation: >-
      The whole of the pharmacological evidence, and it is cell culture in
      human cardiac fibroblasts and a kidney cell line rather than any
      clinical observation.
  - reference: PMID:28503297
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Cardiac compromise is not so common in isolated episodes
    explanation: >-
      PARTIAL, and included because it bears on feasibility rather than on
      mechanism: the target population for a cardiac endpoint trial is a
      minority of infected patients, which is part of why no such study
      exists.
datasets:
- accession: geo:GSE186564
  title: Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4
  description: We found that Histone Deacetylase 4 is the target of human miR-122b-5p using transcriptome approach and report that HDAC4 is downregulated in CHIKV infected human macrophages through global transcriptome profiling
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 18
  publication: PMID:40956096
  notes: Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE300303
  title: Chikungunya virus persists in joint associated macrophages and promotes chronic disease [Xenium]
  data_type: SPATIAL_TRANSCRIPTOMICS
  description: Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus and Ross River virus, cause long-lasting musculoskeletal pain and inflammation. However, the mechanisms driving chronic disease remain unclear. Here, we used single-cell RNA sequencing, spatial transcriptomics and flow cytometry to investigate joint-associated tissues in alphavirus-infected mice at a late stage of infection. We identified an accumulation of inflammatory macrophages in joint-associated tissues with elevated expression of inflammatory markers. These cells harbour CHIKV RNA, suggesting ongoing viral replication during chronic disease.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  sample_count: 6
  publication: PMID:41922840
  notes: Identified by GEO DataSets index search for Chikungunya (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: massive:MSV000096887
  title: Chikungunya replication and infection is dependent upon and alters cellular hexosylceramide levels in Vero cells
  organism:
    preferred_term: African green monkey
    term:
      id: NCBITaxon:60711
      label: Chlorocebus sabaeus
  data_type: METABOLOMICS
  description: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes significant global mor-bidity, including fever, rash, and persistent arthralgia. Utilizing untargeted lipidomics, we investi-gated how CHIKV infection alters host cell lipid metabolism in Vero cells. CHIKV infection induced marked catabolism of hexosylceramides, reducing their levels while increasing ceramide byprod-ucts. Functional studies revealed a reliance on fatty acid synthesis, ?-oxidation, and glycosphin-golipid biosynthesis.
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Chikungunya"). Retrieved 2026-08-02.
- accession: massive:MSV000094494
  title: Chikungunya virus glycoprotein targeting of host factors increases viral fitness in human macrophage
  description: Proteomic analysis of Chikungunya virus E1 and E2 interacting proteins during macrophage infection
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Chikungunya"). Retrieved 2026-08-02.
📚

References & Deep Research

References

17
DOI:10.1002/hsr2.2183
Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives
1 finding
Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives
"Advancements in chikungunya virus management: FDA approval of ixchiq vaccine and global perspectives"
DOI:10.1007/s40259-024-00677-y
Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure
1 finding
Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure
"Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure"
DOI:10.1080/22221751.2024.2362941
Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages
1 finding
Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages
"Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages"
DOI:10.1093/jtm/taae123
From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine
1 finding
Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries.
"Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries."
Show evidence (1 reference)
DOI:10.1093/jtm/taae123 SUPPORT Other
"Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.1186/s12985-025-02721-x
Long-term persistence of serum IgM antibodies against chikungunya virus in patients with chronic arthralgia
1 finding
Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown.
"Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown."
Show evidence (1 reference)
DOI:10.1186/s12985-025-02721-x SUPPORT Human Clinical
"Anti-Chikungunya virus (CHIKV) IgM antibodies may persist for months after infection in some individuals, but the evidence is limited, and their exact duration remains unknown."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.1371/journal.pntd.0011037
Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort
1 finding
Chikungunya-fever (CHIKF) remains a public health major issue.
"Chikungunya-fever (CHIKF) remains a public health major issue."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0011037 SUPPORT Human Clinical
"Chikungunya-fever (CHIKF) remains a public health major issue."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.1371/journal.pntd.0012254
Clinical outcomes of chikungunya: A systematic literature review and meta-analysis
1 finding
Chikungunya is a viral disease caused by a mosquito-borne alphavirus.
"Chikungunya is a viral disease caused by a mosquito-borne alphavirus."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0012254 SUPPORT Other
"Chikungunya is a viral disease caused by a mosquito-borne alphavirus."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.1371/journal.pntd.0012904
Chikungunya virus in Europe: A retrospective epidemiology study from 2007 to 2023
1 finding
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide.
"Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0012904 SUPPORT Human Clinical
"Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is responsible for disease outbreaks worldwide."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3389/fitd.2024.1466207
Excess mortality associated with chikungunya epidemic in Southeast Brazil, 2023
1 finding
The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics.
"The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics."
Show evidence (1 reference)
DOI:10.3389/fitd.2024.1466207 SUPPORT Human Clinical
"The chikungunya virus (CHIKV) was first detected in Brazil in 2014 and has since caused major epidemics."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3390/diagnostics13132306
Performance Evaluation of VIDAS® Diagnostic Assays Detecting Anti-Chikungunya Virus IgM and IgG Antibodies: An International Study
1 finding
Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika.
"Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika."
Show evidence (1 reference)
DOI:10.3390/diagnostics13132306 SUPPORT Human Clinical
"Chikungunya (CHIK) is a debilitating mosquito-borne disease with an epidemiology and early clinical symptoms similar to those of other arboviruses-triggered diseases such as dengue or Zika."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3390/tropicalmed8070365
Chikungunya Virus Diagnosis: A Review of Current Antigen Detection Methods
1 finding
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV).
"Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV)."
Show evidence (1 reference)
DOI:10.3390/tropicalmed8070365 SUPPORT Other
"Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV)."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3390/tropicalmed9100247
Chronic Rheumatologic Disease in Chikungunya Virus Fever: Results from a Cohort Study Conducted in Piedecuesta, Colombia
1 finding
This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia.
"This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia."
Show evidence (1 reference)
DOI:10.3390/tropicalmed9100247 SUPPORT Human Clinical
"This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3390/v18040428
Pathogenesis of Chronic Arthritis Due to Chikungunya Virus and Advances in Vaccine Development
1 finding
Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus.
"Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus."
Show evidence (1 reference)
DOI:10.3390/v18040428 SUPPORT Other
"Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.3390/vaccines13060576
Comprehensive Assessment of Reactogenicity and Safety of the Live-Attenuated Chikungunya Vaccine (IXCHIQ®)
1 finding
This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials.
"This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials."
Show evidence (1 reference)
DOI:10.3390/vaccines13060576 SUPPORT Other
"This overview provides a comprehensive safety evaluation of the approved live-attenuated vaccine VLA1553 (IXCHIQ®) for active immunization for the prevention of disease caused by chikungunya virus (CHIKV) in clinical trials."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.5501/wjv.v13.i2.89985
Long chikungunya? An overview to immunopathology of persistent arthralgia
1 finding
Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years.
"Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years."
Show evidence (1 reference)
DOI:10.5501/wjv.v13.i2.89985 SUPPORT Other
"Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years."
Deep research cited this publication as relevant literature for Chikungunya.
DOI:10.59249/rqyj3197
Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review
1 finding
Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review
"Acute Immunological Profile and Prognostic Biomarkers of Persistent Joint Pain in Chikungunya Fever: A Systematic Review"
DOI:10.7189/jogh.16.04055
Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study
1 finding
Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study
"Global and regional burden of chikungunya from 2004 to 2024: a worldwide observational study"

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.

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Disease Characteristics Research Template
Edison Scientific Literature 41 citations 2026-04-04T13:14:56.619870

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Chikungunya
  • MONDO ID: (if available)
  • Category: Infectious Disease

Research Objectives

Please provide a comprehensive research report on Chikungunya covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Comprehensive Research Report: Chikungunya (Chikungunya fever)

Target disease

  • Disease name: Chikungunya (often “chikungunya fever”) (weber2024chikungunyavirusvaccines pages 1-2, NCT04603131 chunk 2)
  • Category: Infectious disease (arboviral; alphavirus infection) (NCT04603131 chunk 2)

1) Disease information

Overview/definition. Chikungunya is a mosquito-borne viral disease caused by chikungunya virus (CHIKV), an alphavirus, classically presenting with acute fever and prominent arthralgia/arthritis, with a substantial fraction developing persistent arthralgia lasting months to years (“chronic chikungunya”). (weber2024chikungunyavirusvaccines pages 1-2, rama2024clinicaloutcomesof pages 8-11)

Key identifiers and controlled vocabularies (available from retrieved evidence). - MeSH heading: Chikungunya Fever; MeSH ID: D065632 (ClinicalTrials.gov metadata) (NCT04603131 chunk 2, NCT06973772 chunk 3) - MeSH ancestors (examples): Alphavirus Infections; Arbovirus Infections; Mosquito-Borne Diseases; Togaviridae Infections; RNA Virus Infections (NCT04603131 chunk 2)

Synonyms/alternative names in the retrieved sources. - “Chikungunya”, “Chikungunya fever”, “Chikungunya disease” (NCT04603131 chunk 2, rama2024clinicaloutcomesof pages 1-2) - Abbreviations: “CHIK” (disease), “CHIKV” (virus) (weber2024chikungunyavirusvaccines pages 1-2, rama2024clinicaloutcomesof pages 1-2) - Chronic forms described as “chronic chikungunya disease (CCD)” and “chikungunya arthritis” (maurer2025comprehensiveassessmentof pages 29-29)

Identifiers not recovered in the tool-retrieved texts. ICD-10/ICD-11, MONDO, and Orphanet IDs were not present in the retrieved full text excerpts; therefore they are not asserted here from primary evidence. (weber2024chikungunyavirusvaccines pages 1-2, rama2024clinicaloutcomesof pages 1-2)

Evidence source type. This report synthesizes aggregated disease-level resources (systematic reviews/meta-analyses, cohort studies, diagnostic validation studies, regulatory/vaccine development reviews, and ClinicalTrials.gov records), rather than individual EHR-only patient data. (rama2024clinicaloutcomesof pages 8-11, lazari2023clinicalmarkersof pages 1-2, pereira2023performanceevaluationof pages 1-2, chen2024frombenchto pages 2-3, NCT05072080 chunk 2)

2) Etiology

Causal factor. Infection with CHIKV transmitted by Aedes mosquitoes (notably Aedes aegypti and Aedes albopictus) is the proximate cause of chikungunya. (weber2024chikungunyavirusvaccines pages 1-2)

Risk factors (host/clinical). - Female sex increases risk of progression to chronic inflammatory joint disease in a prospective Brazilian cohort (RR 1.52, 95% CI 1.15–1.99). (lazari2023clinicalmarkersof pages 1-2) - Subacute persistence of symptoms (Day 21) and especially articular edema are predictors of chronification beyond 3 months (examples: reported edema RR 3.61; small-joint edema RR 4.22). (lazari2023clinicalmarkersof pages 1-2) - Reviews highlight older age (>35 years) and obesity as correlates of severe/atypical disease presentations. (weber2024chikungunyavirusvaccines pages 1-2)

Protective factors / genetic factors. No robust human protective variants or definitive genetic susceptibility loci were identified in the retrieved evidence set. Mechanistic reviews discuss antiviral interferon responses as protective at the pathway level (see pathophysiology), but not as specific human protective genotypes. (ma2026pathogenesisofchronic pages 6-7, silveirafreitas2024longchikungunya?an pages 2-4)

3) Phenotypes (clinical features)

3.1 Acute chikungunya (typical clinical picture and frequency)

A recent systematic review/meta-analysis (published June 2024) quantified pooled symptom prevalences: arthralgia ~89.7%, fever ~87.8%, myalgia ~62.9%, rash ~44%, and headache ~49.5%; hospitalization during the acute phase was ~17%. (rama2024clinicaloutcomesof pages 8-11, rama2024clinicaloutcomesof media e50a84dc)

Suggested HPO mappings (examples). - Fever: HP:0001945 - Arthralgia: HP:0002829 - Arthritis (inflammatory joint disease): HP:0001369 - Myalgia: HP:0003326 - Rash (maculopapular): HP:0000980 (or HP:0001050 for generalized rash) - Headache: HP:0002315 - Joint swelling/edema: HP:0001382 - Fatigue: HP:0012378

(Phenotype names and frequencies supported by meta-analysis; HPO IDs are standard ontology suggestions for knowledge-base normalization.) (rama2024clinicaloutcomesof pages 8-11)

3.2 Post-acute and chronic chikungunya (arthralgia/arthritis and QoL)

Persistence/chronicity rates (pooled). Symptom persistence declines over time but remains substantial: 43.9% at 3 months, 34.4% at 6 months, and 31.9% at 12 months in pooled estimates. (rama2024clinicaloutcomesof pages 8-11, rama2024clinicaloutcomesof media 900f64f8)

Cohort-based chronic inflammatory joint disease and imaging. In a prospective Brazilian cohort (PLOS NTD; Jan 2023), 45.3% (39/86) of those completing follow-up met criteria for post-chikungunya chronic inflammatory joint disease (pCHIKV-CIJD); among those examined by ultrasound, 90.6% had abnormal findings, with synovitis (65.5%) and joint effusion (58.6%) common. (lazari2023clinicalmarkersof pages 1-2)

Quality-of-life and fatigue impacts. A Colombia cohort study (published Oct 2024) assessed adults seven years after infection: 14.1% had post-CHIKV chronic rheumatism, and chronic fatigue prevalence was 54.6% in that chronic rheumatism group (vs 8.6% in those without rheumatic disease); QoL was significantly worse in groups with chronic rheumatologic/non-inflammatory pain than those without rheumatic disease. (lozanoparra2024chronicrheumatologicdisease pages 1-2)

Suggested HPO mappings for chronic disease. - Synovitis: HP:0100765 - Joint effusion: HP:0002203 - Morning stiffness: HP:0030833 - Chronic fatigue: HP:0012432

(pCHIKV-CIJD imaging and chronic fatigue/QoL supported by cohort studies; HPO IDs are standard ontology suggestions.) (lazari2023clinicalmarkersof pages 1-2, lozanoparra2024chronicrheumatologicdisease pages 1-2)

4) Genetic / molecular information

Chikungunya is not a monogenic inherited disease; host genetics may influence severity/chronicity, but specific causal variants were not retrieved in the current evidence set. (ma2026pathogenesisofchronic pages 7-9)

5) Environmental information

The primary environmental determinant is exposure to competent mosquito vectors (Aedes spp.), with public-health relevance heightened in settings with co-circulating arboviruses (e.g., dengue, Zika) that overlap clinically and diagnostically. (pereira2023performanceevaluationof pages 1-2)

6) Mechanism / pathophysiology (current understanding)

Persistent musculoskeletal disease is widely interpreted as an immunopathologic sequel driven by tissue tropism, inflammatory signaling, and persistence of viral antigen/RNA in joint-related compartments.

Causal chain (high-level): 1) Acute infection and tissue tropism: CHIKV shows tropism for monocytes/macrophages and joint-associated cells (including fibroblasts/synoviocytes), triggering robust innate cytokine and chemokine responses (e.g., IL-6, IL-1β, IL-8, IL-17; CCL2; CXCL9/10). (silveirafreitas2024longchikungunya?an pages 4-5) 2) Innate antiviral pathways and evasion: Type I interferon responses help control replication; CHIKV nonstructural proteins can antagonize interferon signaling, which may contribute to persistence and worse chronic outcomes. (ma2026pathogenesisofchronic pages 6-7) 3) Antigen persistence and macrophage-centered chronic inflammation: Mechanistic synthesis proposes that viral antigens persist post-infection and sustain activation of synovial macrophages, including via SLAMF7, promoting recruitment/infiltration of CD4+ T cells and chronic local cytokine production. (silveirafreitas2024longchikungunya?an pages 1-2) 4) Th17 axis and bone/cartilage injury: Expansion of Th17 responses and IL-17 signaling promotes RANKL upregulation, osteoclastogenesis, bone resorption, and matrix remodeling; persistent proinflammatory cytokines (IL-6/MCP-1) and MMP activation contribute to cartilage extracellular matrix degradation. (silveirafreitas2024longchikungunya?an pages 4-5, lozanoparra2024acuteimmunologicalprofile pages 8-10)

Suggested Cell Ontology (CL) terms (examples). - Macrophage: CL:0000235 - Monocyte: CL:0000576 - CD4-positive, alpha-beta T cell: CL:0000624 - T helper 17 cell: CL:0000899

Suggested GO Biological Process terms (examples). - Type I interferon signaling pathway - Inflammatory response - Positive regulation of cytokine production - Osteoclast differentiation - Extracellular matrix disassembly

(Mechanistic claims supported by 2024 immunopathology review and 2024 systematic review of immunologic biomarkers; terms are ontology suggestions for knowledge-base normalization.) (silveirafreitas2024longchikungunya?an pages 1-2, lozanoparra2024acuteimmunologicalprofile pages 8-10)

7) Anatomical structures affected

Primary morbidity is musculoskeletal/joint involvement (synovium and peri-articular tissues) with imaging evidence of synovitis and effusion in chronic inflammatory joint disease. (lazari2023clinicalmarkersof pages 1-2)

Suggested UBERON terms (examples). - Synovial membrane: UBERON:0002390 - Joint: UBERON:0000982

8) Temporal development (onset and progression)

Chikungunya is typically acute onset, with prominent symptoms during the first 7–10 days, but a substantial fraction progress to persistent/chronic arthralgia over months to years. Pooled chronicity at 3–12 months remains ~32–44%. (rama2024clinicaloutcomesof pages 8-11, rama2024clinicaloutcomesof media 900f64f8)

9) Inheritance and population (epidemiology)

9.1 Global and regional burden (recent)

A worldwide observational study estimating 2024 autochthonous burden reported 696,564 cases globally (incidence 11.13/100,000) and that the Americas carried the largest burden (431,305 cases; 43.90/100,000). (wang2026globalandregional pages 4-5)

9.2 2023–2024 outbreak examples and surveillance gaps

  • Brazil (Minas Gerais, 2023): Excess-mortality analysis estimated 890 excess deaths attributable to chikungunya in a ~2.5 million population area (mortality rate 35.1/100,000), compared with only 15 confirmed deaths in surveillance in that area—suggesting major under-ascertainment. (freitas2024excessmortalityassociated pages 1-2)
  • Argentina (2023): 2,314 confirmed cases (EW1–43) with genomic evidence of ECSA lineage predominance, representing lineage shift compared with earlier Asian-lineage circulation (2016). (fabbri2024tracingtheevolution pages 1-2)
  • Europe (2007–2023 surveillance summary): 4,730 cases documented in 2007–2022 across mainland Europe, and no cases reported in 2023; most historical cases were travel-related. (liu2025chikungunyavirusin pages 1-2)

10) Diagnostics

10.1 Recommended diagnostic windows (molecular vs serology)

Guidance summarized in a 2023 international evaluation study supports: - rRT-PCR within the first week of illness (confirmatory), with rRT-PCR alone days 0–5, and rRT-PCR ± IgM days 5–7; after day 7, serology becomes central. (pereira2023performanceevaluationof pages 2-3) - After day 7, IgM positivity is presumptive, and paired sera IgG seroconversion or ≥4-fold rise confirms active infection; IgG may persist for years. (pereira2023performanceevaluationof pages 2-3)

10.2 Performance data (recent)

  • Automated VIDAS® assays showed high agreement with comparator ELISA (97.5–100%), with IgM positive detection 88.2–100% ≥5 days post symptom onset and IgG detection 100% ≥11 days; analytical cross-reactivity was low (≤2.9% overall). (pereira2023performanceevaluationof pages 15-16)
  • Antigen-detection methods (reviewed 2023) can perform well early: antigen detection sensitivity reported ~85% overall and up to ~95% in the first 5 days in some evaluations; selected rapid tests reported sensitivity/specificity around 89.4%/94.4%. (simo2023chikungunyavirusdiagnosis pages 4-6)
  • Longitudinal cohort evidence (2025) demonstrates that IgM can persist far beyond typical expectations: among patients with chronic arthralgia, 33% remained IgM-positive >720 days post symptom onset, complicating surveillance and interpretation of single-sample IgM. (jacobnascimento2025longtermpersistenceof pages 5-7)

Differential diagnosis. Because clinical presentation overlaps with dengue and Zika (especially during co-circulation), diagnostic algorithms emphasize early RT-PCR and careful interpretation of serology. (pereira2023performanceevaluationof pages 1-2)

11) Outcome / prognosis

Chronic morbidity. Pooled chronicity rates are substantial at 3–12 months (43.9% → 31.9%), with cohort evidence of chronic inflammatory arthritis syndromes and QoL impairment. (rama2024clinicaloutcomesof pages 8-11, lazari2023clinicalmarkersof pages 1-2)

Mortality. Meta-analysis estimated overall mortality around 0.32% in general/low-risk populations, but much higher mortality estimates in hospitalized/elderly/high-risk subgroups. (rama2024clinicaloutcomesof pages 8-11, rama2024clinicaloutcomesof media 3fb5798c)

Surveillance under-ascertainment of death. Excess mortality analysis in Brazil (2023) indicates routine surveillance may severely underestimate chikungunya-attributable mortality during epidemics. (freitas2024excessmortalityassociated pages 1-2)

12) Treatment

No specific antivirals. Multiple reviews note there is no FDA-approved CHIKV-specific antiviral medication, and clinical management is primarily supportive/symptomatic. (irfan2024advancementsinchikungunya pages 1-2, maurer2025comprehensiveassessmentof pages 1-2)

Acute symptomatic management (real-world). Supportive care includes rest, hydration, analgesics and NSAIDs. (weber2024chikungunyavirusvaccines pages 1-2)

Chronic inflammatory arthritis management (real-world). For persistent inflammatory manifestations, treatments include NSAIDs and corticosteroids; DMARDs such as methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine are used when disease resembles RA-like inflammatory arthritis, with TNF inhibitors (e.g., etanercept) reported for refractory cases. (silveirafreitas2024longchikungunya?an pages 2-4)

Suggested MAXO mappings (examples). - Vaccination: MAXO:0000102 (immunization/vaccination) - NSAID therapy: (MAXO class “drug therapy” + NSAID) - Corticosteroid therapy: (MAXO class “drug therapy” + glucocorticoid) - DMARD therapy (methotrexate/sulfasalazine/leflunomide/hydroxychloroquine): (MAXO class “drug therapy”) - TNF inhibitor therapy: (MAXO class “biologic therapy”)

(MAXO IDs can vary by release; the above are suggested mapping categories for knowledge-base annotation.)

13) Prevention

13.1 Vaccine-based prevention (major 2023–2024 development)

IXCHIQ (VLA1553) approvals. The live-attenuated single-dose vaccine IXCHIQ was approved by the US FDA (Nov 2023), Health Canada (Jun 2024), and the European Commission (Jul 2024). (weber2024chikungunyavirusvaccines pages 1-2)

IXCHIQ immunogenicity (phase 3, surrogate endpoint). A Journal of Travel Medicine development review (published/accepted in 2024) reports seroresponse of 98.9% at Day 28 and durable seroconversion at 6 months (98.3%). (chen2024frombenchto pages 2-3)

IXCHIQ safety/reactogenicity (pooled trial evidence). Solicited systemic events were common but mostly short-lived: fever 13.5%, arthralgia 17.2%, myalgia 23.9%, fatigue 28.5%, headache 31.6%. Broad-definition AESIs were 11.7% in vaccine vs 0.6% placebo; prolonged AESIs (≥30 days) occurred in 0.5% and severe cases in 1.6% of vaccine recipients in the cited pooled analysis. (maurer2025comprehensiveassessmentof pages 1-2)

13.2 Vector control and bite avoidance

When vaccines are unavailable or for broader population control, prevention relies on reducing mosquito breeding sites and avoiding bites (repellents, protective clothing, screens). (weber2024chikungunyavirusvaccines pages 1-2)

14) Other species / natural disease

The retrieved evidence set did not provide primary data on naturally occurring disease in non-human vertebrate species beyond experimental models; thus, non-human natural-host epidemiology is not asserted here. (chen2024frombenchto pages 2-3)

15) Model organisms

Vaccine and pathogenesis research commonly uses: - Mouse models (immunogenicity, viremia, clinical signs) (weber2024chikungunyavirusvaccines pages 2-4) - Non-human primates (e.g., cynomolgus macaques) for immunogenicity, challenge protection, and establishing a serological surrogate of protection used for accelerated vaccine development. (chen2024frombenchto pages 2-3)

Recent developments and real-world implementations (2023–2024 emphasis)

  • 2024 meta-analysis consolidated pooled estimates of acute symptom frequencies, chronicity at 3–12 months, hospitalization, and mortality, providing a quantitative baseline for burden estimation and policy. (rama2024clinicaloutcomesof pages 8-11, rama2024clinicaloutcomesof media e50a84dc)
  • 2023–2024 marks transition from “no licensed vaccines” to first approved vaccine (IXCHIQ) and active late-stage development of VLP vaccines. (weber2024chikungunyavirusvaccines pages 1-2, NCT05072080 chunk 2)
  • 2024 excess-mortality analyses underscore that chikungunya mortality may be substantially underestimated during epidemics, influencing prioritization for vaccination and surveillance strengthening. (freitas2024excessmortalityassociated pages 1-2)

Clinical trials snapshot (real-world pipeline)

  • PXVX0317 (VLP vaccine), Phase 3: NCT05072080 (Bavarian Nordic). (NCT05072080 chunk 2)
  • PXVX0317, Phase 2: NCT03992872, open-label, alum-adjuvanted VLP vaccine; results posted 2024-10-16. (NCT03992872 chunk 1)
  • Dengue + chikungunya co-administration, Phase 3b: NCT06973772 (Butantan Institute), planned start 2026-03-31; evaluates coadministration of Butantan-DV and live-attenuated chikungunya vaccine. (NCT06973772 chunk 1)

Evidence table (key statistics)

Metric Value Population/Context Source (DOI + month/year) Notes
Acute arthralgia prevalence 89.7% Pooled symptomatic chikungunya cases in systematic review/meta-analysis 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Acute hallmark symptom
Acute fever prevalence 87.8% Pooled symptomatic chikungunya cases 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Common early presentation
Acute myalgia prevalence 62.9% Pooled symptomatic chikungunya cases 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Often accompanies fever/arthralgia
Acute rash prevalence ~44% Pooled symptomatic chikungunya cases 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Maculopapular rash commonly reported
Acute headache prevalence ~49.5% Pooled symptomatic chikungunya cases 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Non-specific but frequent
Hospitalization rate ~17% Acute-phase chikungunya cases 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Heterogeneous across studies
Chronicity at 3 months 43.9% Post-acute/chronic symptom persistence 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Chronic arthralgia declines over time
Chronicity at 6 months 34.4% Post-acute/chronic symptom persistence 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Persistent burden remains substantial
Chronicity at 12 months 31.9% Post-acute/chronic symptom persistence 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Consistent with long-term sequelae burden
Mortality rate 0.32% General/low-risk pooled estimate 10.1371/journal.pntd.0012254, Jun 2024 (rama2024clinicaloutcomesof pages 8-11) Higher in hospitalized/elderly/high-risk groups
2023 Brazil excess mortality estimate 890 excess deaths; 35.1/100,000 North and Northeast macroregions of Minas Gerais, Brazil; 2023 epidemic 10.3389/fitd.2024.1466207, Oct 2024 (freitas2024excessmortalityassociated pages 1-2, freitas2024excessmortalityassociated pages 5-7) ~60-fold above deaths captured by surveillance in study region
2024 global burden 696,564 autochthonous cases; 11.13/100,000 incidence Global 10.7189/jogh.16.04055, Feb 2026 (wang2026globalandregional pages 4-5) Americas: 431,305 cases; 43.90/100,000
2023 Argentina outbreak 2,314 confirmed cases; ECSA genotype predominated Argentina, EW1–43 2023 10.1080/22221751.2024.2362941, Jun 2024 (fabbri2024tracingtheevolution pages 1-2) 2016 epidemic had Asian lineage; 2023 shifted to ECSA
2023 Europe cases 0 cases reported in 2023; 4,730 total in 2007–2022 Mainland Europe surveillance 10.1371/journal.pntd.0012904, Mar 2025 (liu2025chikungunyavirusin pages 1-2) Most historic European cases were travel-related
Diagnostic timing: RT-PCR vs serology RT-PCR ≤7 days; RT-PCR alone days 0–5; RT-PCR ± IgM days 5–7; serology after day 7 Laboratory diagnosis of acute vs later infection 10.3390/diagnostics13132306, Jul 2023 (pereira2023performanceevaluationof pages 2-3, pereira2023performanceevaluationof pages 15-16) Paired IgG seroconversion or ≥4-fold rise confirms active infection after day 7
VIDAS IgM detection window 88.2–100.0% positive at ≥5 days post-symptom onset Proven CHIKV infection 10.3390/diagnostics13132306, Jul 2023 (pereira2023performanceevaluationof pages 15-16, pereira2023performanceevaluationof pages 1-2) Agreement with ELISA 97.5–100%
VIDAS IgG detection window 100.0% positive at ≥11 days post-symptom onset Proven CHIKV infection 10.3390/diagnostics13132306, Jul 2023 (pereira2023performanceevaluationof pages 15-16, pereira2023performanceevaluationof pages 1-2) Useful for later diagnosis/surveillance
IgM persistence >2 years 33% (7/21) remained IgM-positive >720 DPSO Patients with chronic arthralgia 10.1186/s12985-025-02721-x, Apr 2025 (jacobnascimento2025longtermpersistenceof pages 1-2, jacobnascimento2025longtermpersistenceof pages 5-7) Positive IgM may not indicate recent infection
IXCHIQ approval dates US FDA: Nov 2023; Health Canada: Jun 2024; European Commission: Jul 2024 Regulatory approvals for VLA1553/IXCHIQ 10.1007/s40259-024-00677-y, Sep 2024 (weber2024chikungunyavirusvaccines pages 1-2); 10.1007/s40259-024-00677-y, Sep 2024 (weber2024chikungunyavirusvaccines pages 1-2) First licensed chikungunya vaccine
IXCHIQ phase 3 seroresponse 98.9% at Day 28; 98.3% maintained seroconversion at 6 months Pivotal phase 3, n=4,128 10.1093/jtm/taae123, Sep 2024 (chen2024frombenchto pages 2-3) Immune responses similar in older adults
IXCHIQ reactogenicity Fever 13.5%; arthralgia 17.2%; myalgia 23.9%; fatigue 28.5%; headache 31.6% Pooled VLA1553 clinical-trial safety data 10.3390/vaccines13060576, May 2025 (maurer2025comprehensiveassessmentof pages 1-2) Broad AESIs 11.7%; prolonged AESIs 0.5%; severe cases 1.6%
PXVX0317 phase 3 trial NCT05072080 VLP-based chikungunya vaccine, sponsor Bavarian Nordic ClinicalTrials.gov, 2021 entry (NCT05072080 chunk 2) Phase 3 placebo-controlled study with immunogenicity endpoints at Days 8, 15, 22, 183

Table: This table compiles the most important quantitative clinical, epidemiologic, diagnostic, and vaccine-development metrics for chikungunya from the gathered evidence. It is useful as a quick-reference summary for populating a disease knowledge base or supporting a narrative research report.

Visual evidence from meta-analysis

Key pooled estimates and forest plots for chronicity, mortality, and symptomatic rate are presented in the meta-analysis Table/Figures. (rama2024clinicaloutcomesof media e50a84dc, rama2024clinicaloutcomesof media 900f64f8, rama2024clinicaloutcomesof media 3fb5798c, rama2024clinicaloutcomesof media 32d1ac79)

Abstract quotes supporting key claims (verbatim from retrieved abstracts)

  • “Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63–84%), the chronicity rate was 44% (95% CI: 31–57%), and the mortality rate was 0.3% (95% CI: 0.1–0.7%).” (PLOS NTD meta-analysis; published Jun 2024) (rama2024clinicaloutcomesof pages 1-2)
  • “In 2023, a major chikungunya epidemic occurred in Minas Gerais… During the epidemic, there were 890 excess deaths attributed to chikungunya, translating into a mortality rate of 35.1/100,000 inhabitants.” (Frontiers in Tropical Diseases; Oct 2024) (freitas2024excessmortalityassociated pages 1-2)
  • “In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ.” (BioDrugs review; Sep 2024) (weber2024chikungunyavirusvaccines pages 1-2)

Notes on evidence limitations for knowledge-base curation

  • This evidence set supports MeSH normalization (D065632) but did not contain ICD-10/ICD-11/MONDO/Orphanet IDs in accessible text; adding those identifiers requires consultation of coding/ontology resources beyond the retrieved papers. (NCT04603131 chunk 2, weber2024chikungunyavirusvaccines pages 1-2)
  • Human genetic susceptibility or protective variants were not identified in the retrieved corpus; mechanistic susceptibility is supported at pathway/cell-type level rather than variant level. (ma2026pathogenesisofchronic pages 6-7, silveirafreitas2024longchikungunya?an pages 2-4)

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