Tularemia

Infectious Disease MONDO:0018077 Pathograph 19 Show in embeddings browser Bacterial Infection Zoonotic Disease Tick-Borne Disease

Tularemia is a highly infectious zoonotic disease caused by the intracellular Gram-negative bacterium Francisella tularensis. Humans acquire infection through arthropod (tick or mosquito) bites, direct contact with infected animals (especially rabbits, hares, and rodents), ingestion of contaminated food or water, or inhalation of infectious aerosols; person-to-person transmission has not been reported. After uptake by macrophages, F. tularensis escapes the phagosome into the cytosol via the Francisella Pathogenicity Island-encoded type VI secretion system, where it replicates and triggers caspase-1 inflammasome activation and granulomatous inflammation. The route of inoculation determines the clinical form: ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal tularemia. F. tularensis requires as few as 10 organisms to cause disease and is classified as a Category A bioterrorism agent.

Ask OpenScientist

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

Submitting...

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

◆

Subtypes

6
Glandular tularemia MONDO:0000320
15.8%
Localized tularemia form with acute flu-like symptoms and marked regional lymphadenopathy after arthropod or animal inoculation but without the visible cutaneous inoculation ulcer that defines the ulceroglandular form.
Show evidence (2 references)
PMID:37916743 SUPPORT REVIEW SYNTHESIS Human clinical
"In glandular form, there are no skin ulcers but lymphadenopathy is marked"
The review distinguishes glandular tularemia from ulceroglandular tularemia by the absence of a skin ulcer and the presence of marked lymphadenopathy.
PMID:23104256 SUPPORT Human clinical
"Patients had clinical presentations compatible with oropharyngeal (74 %), glandular (15.8 %), and oculoglandular (5.0 %) tularemia."
This Central Anatolia cohort observed the glandular clinical form in 15.8% of confirmed tularemia patients.
Ulceroglandular tularemia MONDO:0001413
Cutaneous-entry form with an inoculation-site ulcer and painful regional lymphadenopathy after arthropod bite or infected-animal handling. Curated as a standalone entry, Ulceroglandular_Tularemia (MONDO:0001413), which carries the cutaneous-inoculation to ulcer-and-regional-node mechanism.
Oculoglandular tularemia MONDO:0001665
5.0%
Conjunctival-entry form with granulomatous conjunctivitis and ipsilateral preauricular, submandibular, or cervical lymphadenopathy. Curated as a standalone entry, Oculoglandular_Tularemia (MONDO:0001665), which carries the conjunctival-inoculation to ocular-and-regional-node mechanism.
Show evidence (1 reference)
PMID:23104256 SUPPORT Human clinical
"Patients had clinical presentations compatible with oropharyngeal (74 %), glandular (15.8 %), and oculoglandular (5.0 %) tularemia."
This Central Anatolia cohort observed the oculoglandular clinical form in 5.0% of confirmed tularemia patients.
Pneumonic tularemia MONDO:0002212
Inhalational form with pulmonary Francisella tularensis infection and acute pneumonic inflammation. Curated as a standalone entry, Pneumonic_Tularemia (MONDO:0002212), which carries the aerosol exposure to macrophage escape, inflammasome sensing, and inflammatory pneumonia mechanism.
Typhoidal tularemia MONDO:0000321
14.4%
Systemic bacteremic tularemia form without a dominant primary localizing lesion; curated as Typhoidal_Tularemia (MONDO:0000321), which carries the multisite Francisella-entry route, bacteremic sepsis-like mechanism, and typhoidal treatment and diagnostic claims.
Show evidence (2 references)
PMID:40107886 SUPPORT REVIEW SYNTHESIS Other
"the multiple routes of infection result in six typical clinical pictures (ulceroglandular, glandular, oculoglandular, oropharyngeal, typhoidal, and pneumonic)"
Identifies typhoidal tularemia as one of the canonical clinical forms that result from the multiple Francisella acquisition routes.
PMID:24874046 SUPPORT Human clinical
"Overall, oropharyngeal tularaemia (41.1 %) was the most common clinical presentation, followed by glandular (14.4 %), typhoidal (14.4 %), respiratory (13.3 %) and ulceroglandular (12.8 %) tularaemia."
This high-incidence Norwegian surveillance year observed the typhoidal clinical form in 14.4% of tularemia patients.
Gastrointestinal tularemia MONDO:0001916
Enteric form acquired by ingestion of contaminated food or water; curated as Gastrointestinal_Tularemia (MONDO:0001916), which carries the ingestion portal of entry and the alimentary and draining-node inflammatory mechanism.
Show evidence (1 reference)
PMID:19835784 SUPPORT BACKGROUND Human clinical
"Francisella tularensis is a Gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia in humans from ingestion of contaminated food or water."
Names gastrointestinal tularemia as a human clinical form of F. tularensis infection acquired by ingestion.
⚙

Pathophysiology

7
Arthropod-Borne and Zoonotic Acquisition
Humans acquire F. tularensis through arthropod bites (ticks and mosquitoes), handling of infected animals, ingestion of contaminated food or water, or inhalation of contaminated aerosols. The route of entry determines the resulting clinical form.
Phagocytosis GO:0006909 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Phagocytosis (GO:0006909). GO:0006909 is a biological process from the Gene Ontology.
Downstream
Macrophage Phagosomal Escape and Cytosolic Replication Following inoculation, F. tularensis is taken up by macrophages, where it establishes its intracellular replicative niche.
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals, oculo-glandular form as a result of conjunctival infection, and oro-pharyngeal form by intake of contaminated food or water."
Establishes that the route of inoculation determines the clinical form of tularemia.
PMID:37941380 SUPPORT Other
"Depending on its entry route into the organism, F. tularensis causes different diseases, ranging from life-threatening pneumonia to less severe ulceroglandular tularaemia."
Confirms entry route determines disease severity and clinical form.
Macrophage Phagosomal Escape and Cytosolic Replication
F. tularensis enters macrophages by looping phagocytosis. The Francisella-containing phagosome matures transiently before the bacterium escapes into the cytosol within 30-60 minutes via the Francisella Pathogenicity Island-encoded type VI secretion system (T6SS), then proliferates in the cytosol. The T6SS and its effectors are the main virulence attribute promoting phagosomal escape.
Macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
Suppression of host phagosome maturation GO:0141158 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Suppression of host phagosome maturation, annotated with symbiont-mediated suppression of host phagosome maturation (GO:0141158). GO:0141158 is a biological process from the Gene Ontology. Symbiont entry into host GO:0044409 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Symbiont entry into host (GO:0044409). GO:0044409 is a biological process from the Gene Ontology.
Downstream
Inflammasome Activation and Granulomatous Inflammation Cytosolic replication of F. tularensis is sensed by the host innate immune system, triggering caspase-1 inflammasome activation and a pro-inflammatory, granulomatous response.
Lymphatic Francisella Spread to Regional Nodes Organisms introduced through skin or mucosa can drain from the inoculation territory into the regional lymph node basin.
Show evidence (3 references)
PMID:37941380 SUPPORT Other
"The main virulence attribute of F. tularensis is the type 6 secretion system (T6SS) and its effectors that promote escape from the phagosome."
Identifies the FPI-encoded T6SS as the principal virulence factor mediating phagosomal escape.
PMID:19863554 SUPPORT Other
"Entry of F. tularensis into macrophages is mediated by looping phagocytosis"
Describes the looping phagocytosis mechanism of macrophage entry.
PMID:19863554 SUPPORT Other
"The Francisella pathogenicity island, which potentially encodes a putative type VI secretion system, is essential for phagosome biogenesis and bacterial escape into the cytosol within macrophages and arthropod-derived cells."
Confirms the FPI/T6SS is essential for bacterial escape into the macrophage cytosol.
Lymphatic Francisella Spread to Regional Nodes
After peripheral inoculation, F. tularensis drains through lymphatics into the regional node basin, anatomically localizing glandular and ulceroglandular tularemia as painful regional lymphadenitis.
inflammatory response GO:0006954 ↑ INCREASED 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.
lymph node UBERON:0000029 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lymph node (UBERON:0000029). UBERON:0000029 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Necrotizing and Suppurative Granulomatous Lymphadenitis Node infection drives granulomatous and suppurative tissue inflammation.
Show evidence (1 reference)
PMID:37941380 SUPPORT REVIEW SYNTHESIS Human clinical
"Later, one or more chronically evolving lymphadenopathies can develop in the lymphatic system draining the site of entry."
The Francisella review connects the portal of entry to later lymphadenopathy in the draining lymphatic basin.
Necrotizing and Suppurative Granulomatous Lymphadenitis
Node-localized tularemia produces granulomas, necrosis, abscess-forming suppuration, and extracapsular inflammation; fluctuant infected nodes can require fine-needle aspiration, drainage, or excision.
inflammatory response GO:0006954 ↑ INCREASED 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.
lymph node UBERON:0000029 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lymph node (UBERON:0000029). UBERON:0000029 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Lymphadenopathy Granulomatous and suppurative node inflammation produces painful regional lymph node enlargement.
Show evidence (1 reference)
PMID:23763361 SUPPORT Human clinical
"On histopathology; granulomas, necrosis, and suppurative inflammation extending extracapsular areas were seen."
Human node cytology and resection specimens establish granulomatous, necrotizing, suppurative lymphadenitis as a tularemia tissue pattern.
Inflammasome Activation and Granulomatous Inflammation
Cytosolic sensing of F. tularensis triggers IRF-3-dependent IFN-beta secretion and activation of the caspase-1 inflammasome with a pro-inflammatory response. The resulting inflammation produces granulomatous lesions and the systemic and localized clinical manifestations of tularemia, including fever, regional lymphadenopathy, skin ulceration, and pneumonia.
Macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
Inflammasome-mediated signaling GO:0141084 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Inflammasome-mediated signaling, annotated with inflammasome-mediated signaling pathway (GO:0141084). GO:0141084 is a biological process from the Gene Ontology. Inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
Downstream
Fever Systemic inflammation produces fever, the most consistent finding across tularemia forms.
Headache Systemic inflammation contributes to headache in the flu-like prodrome.
Myalgia Systemic inflammation contributes to myalgia in the flu-like prodrome.
Lymphadenopathy Regional inflammation produces lymph node enlargement, the hallmark of glandular and ulceroglandular forms.
Skin Ulcer Inflammation at a cutaneous inoculation site produces the ulcer of ulceroglandular tularemia.
Pneumonia Inflammation following inhalational exposure produces pneumonic tularemia.
Chills Systemic inflammatory cytokines drive the chills of the early flu-like phase.
Show evidence (1 reference)
PMID:19863554 SUPPORT Other
"activation of the inflammasome mediated by caspase-1, and a pro-inflammatory response"
Establishes caspase-1 inflammasome activation and a pro-inflammatory response as the host innate response to cytosolic F. tularensis.
Francisella Ribosomal Translation
Francisella depends on bacterial 70S ribosomal translation for protein synthesis; aminoglycosides and tetracyclines used for tularemia act on this conserved bacterial ribosomal target.
translation GO:0006412 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves translation (GO:0006412). GO:0006412 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:24336183 SUPPORT Other
"The ribosome is one of the main antibiotic targets in the bacterial cell."
Review support for the shared bacterial-ribosome target of aminoglycosides and tetracyclines.
Francisella DNA Gyrase and Topoisomerase IV
F. tularensis requires bacterial type II topoisomerases to control DNA supercoiling and chromosome segregation; fluoroquinolones used for tularemia trap gyrase/topoisomerase-DNA cleavage complexes at this druggable target.
DNA topological change GO:0006265 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves DNA topological change (GO:0006265). GO:0006265 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:27449972 SUPPORT Other
"Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity."
Review support for the bacterial DNA gyrase/topoisomerase IV target of fluoroquinolones.
⬡

Pathograph

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

7
Cardiovascular 1
Lymphadenopathy HP:0002716 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lymphadenopathy (HP:0002716). HP:0002716 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
Glandular and ulceroglandular forms are defined by regional lymphadenopathy following arthropod or animal exposure.
PMID:38294108 SUPPORT Human clinical
"The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease."
CDC systematic review of 870 human cases confirms glandular and ulceroglandular (lymphadenopathy-defined) forms are among the most common.
Immune 1
Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Pulmonary form appears after inhalation of bacteria."
The pulmonary (pneumonic) form of tularemia follows inhalational exposure.
PMID:38294108 SUPPORT Human clinical
"The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease."
CDC systematic review confirms pneumonic disease is among the most common clinical forms of human tularemia.
Integument 1
Skin Ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
This finding defines the ulceroglandular form and is absent by definition in the MONDO:0000320 glandular form.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
The ulceroglandular form is characterized by a skin ulcer at the inoculation site.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia that may or may not include lymphadenopathy."
Review describes the early flu-like (febrile) presentation of tularemia preceding localized findings.
Nervous System 1
Headache HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37941380 SUPPORT REVIEW SYNTHESIS Human clinical
"At onset, tularaemia symptoms are non-specific and include a flu-like syndrome with fever, headache, muscle and joint aches (myalgia, and/or arthralgia)."
Review evidence that headache is part of the early nonspecific influenza-like tularemia syndrome.
Constitutional 2
Chills HP:0025143 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chills (HP:0025143). HP:0025143 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia"
The early flu-like illness of tularemia includes constitutional symptoms such as chills.
Myalgia HP:0003326 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myalgia (HP:0003326). HP:0003326 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37941380 SUPPORT REVIEW SYNTHESIS Human clinical
"At onset, tularaemia symptoms are non-specific and include a flu-like syndrome with fever, headache, muscle and joint aches (myalgia, and/or arthralgia)."
Review evidence that myalgia is part of the early nonspecific influenza-like tularemia syndrome.
💊

Medical Actions

4
Streptomycin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: streptomycin CHEBI:17076 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses streptomycin (CHEBI:17076). CHEBI:17076 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Aminoglycoside, historically the first-line agent for tularemia. In a CDC systematic review of human cases, aminoglycosides were associated with a low fatality rate (0.7%).
Mechanism Target:
INHIBITS Francisella Ribosomal Translation — Streptomycin is an aminoglycoside that treats tularemia by acting at the bacterial ribosome.
Show evidence (1 reference)
PMID:38294108 SUPPORT Human clinical
"Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation."
CDC systematic review confirms aminoglycosides (e.g., streptomycin) are effective for tularemia.
Ciprofloxacin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ciprofloxacin CHEBI:100241 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ciprofloxacin (CHEBI:100241). CHEBI:100241 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Fluoroquinolone used for tularemia. In the CDC systematic review, patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of complications.
Mechanism Target:
INHIBITS Francisella DNA Gyrase and Topoisomerase IV — Ciprofloxacin is a fluoroquinolone that treats tularemia through the conserved bacterial type-II-topoisomerase target.
Show evidence (1 reference)
PMID:38294108 SUPPORT Human clinical
"For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials."
CDC systematic review notes ciprofloxacin may have advantages for pneumonic tularemia.
Doxycycline
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: doxycycline CHEBI:50845 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses doxycycline (CHEBI:50845). CHEBI:50845 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Tetracycline-class agent used for tularemia. Tetracyclines were associated with effective treatment across clinical forms but with higher relapse rates than bactericidal agents.
Mechanism Target:
INHIBITS Francisella Ribosomal Translation — Doxycycline is a tetracycline that treats tularemia by acting at the bacterial ribosome.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"Treatment for tularemia typically entails use of quinolones, tetracyclines, or aminoglycosides."
Review lists tetracyclines (e.g., doxycycline) among the standard antimicrobial classes for tularemia.
Fine-Needle Aspiration or Surgical Drainage
Platform: Surgery
Fluctuant or necrotic tularemia lymph nodes may require fine-needle aspiration, surgical drainage, or excision as adjunctive source control.
Mechanism Target:
Necrotizing and Suppurative Granulomatous Lymphadenitis — Needle aspiration, drainage, and excision remove the suppurative lymph-node compartment responsible for persistent regional disease.
Show evidence (1 reference)
PMID:23104256 SUPPORT Human clinical
"Fine-needle aspiration (FNA) or surgical drainage of fluctuant lymph nodes were performed in 51 (39 %) patients."
The prospective Central Anatolia series documents node aspiration or drainage in 39% of confirmed tularemia cases with fluctuant nodes.
🌍

Environmental Factors

1
Arthropod and infected-animal contact
Tick, mosquito, and other arthropod bites or direct handling of infected animals are exposure routes that can inoculate F. tularensis into skin and soft tissue, triggering ulceroglandular or glandular tularemia.
Show evidence (1 reference)
PMID:37916743 SUPPORT REVIEW SYNTHESIS Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
The review identifies the external exposures that lead to the localized glandular and ulceroglandular forms.
Mechanism Target:
TRIGGERS Arthropod-Borne and Zoonotic Acquisition — Arthropod or animal contact introduces F. tularensis at the portal of entry, initiating the macrophage infection chain.
Show evidence (1 reference)
PMID:37916743 SUPPORT REVIEW SYNTHESIS Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
The review identifies arthropod bite and infected-animal handling as acquisition routes for the glandular and ulceroglandular forms.
🔬

Diagnosis

3
Serology or Microagglutination Testing
Tularemia is commonly confirmed serologically by a positive microagglutination test or by seroconversion on paired sera when the first sample is negative early in the course. Serology should be considered when a cervical lymphadenitis syndrome fails beta-lactam treatment, because delayed appropriate therapy is associated with poorer outcomes.
Diagnostic serology and microagglutination testing NCIT:C217458 NCI Thesaurus (NCIT)
Francisella tularensis antibody serology LOINC:93715-1 Logical Observation Identifiers Names and Codes (LOINC)
Show evidence (3 references)
PMID:22090310 SUPPORT Human clinical
"with fever, sore throat, cervical mass and failure to respond to beta-lactam antibiotics, were followed up with the preliminary diagnosis of tularemia."
Central Anatolia clinicians escalated cervical lymphadenitis cases with beta-lactam nonresponse to suspected tularemia, supporting the diagnostic implication of intrinsic beta-lactam resistance.
PMID:22090310 SUPPORT Human clinical
"The patients who applied to the hospital within 10 days of the initiation of the symptoms were treated successfully, while the others that applied later were not."
The same case series links early presentation with successful treatment, supporting diagnostic delay as a modifiable driver of morbidity.
PMID:22090310 SUPPORT Human clinical
"All of the 8 patients who had negative results in their first samples (< 1/160), revealed seroconversion in their second samples."
The outbreak case series illustrates paired-serum microagglutination diagnosis, including later seroconversion after initially negative tests.
Francisella PCR on Lesional or Node Specimens
PCR detection of F. tularensis DNA in wound or lymph-node material can confirm tularemia before seroconversion and can outperform culture, which is insensitive and hazardous for laboratories.
Francisella PCR on lesional or node specimens NCIT:C17003 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:10618057 SUPPORT Human clinical
"Of 40 patients with culture- and/or serology-verified ulceroglandular tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas culture detected bacterial growth in 25 (62%) patients."
Direct comparison in human ulceroglandular tularemia supports PCR as a more sensitive direct detection method than culture.
Lymph-Node Fine-Needle Aspiration and Histopathology
Fine-needle aspiration of cervical nodes can show suppurative, granulomatous lymphadenitis and provide material for PCR or culture.
Lymph-node fine-needle aspiration and histopathology NCIT:C15361 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:23763361 SUPPORT Human clinical
"However FNA cytology is helpful in differential diagnosis of tularemia and other diseases presented with suppurative, granulomatous cervical lymphadenitis."
Multicenter experience with 53 aspirates supports FNA cytology as a differential-diagnostic test for suppurative granulomatous tularemia lymphadenitis.
🌍

Epidemiology

1
Regional seroprevalence (WHO-EMRO)
Tularemia is endemic across the Northern Hemisphere and is re-emerging in many countries. A 2024 systematic review and meta-analysis of the WHO Eastern Mediterranean Region estimated a human seroprevalence of 6.2%, with the pathogen also detected in environmental samples, ticks, rodents, and domestic ruminants.
Show evidence (1 reference)
PMID:38728365 SUPPORT Human clinical
"The human seroprevalence of tularemia in WHO-EMRO countries was 6.2%"
Meta-analysis quantifies regional human seroprevalence of tularemia.
🦠

Infectious Agent

1
Francisella tularensis
Tularemia is caused by the Gram-negative coccobacillus Francisella tularensis. Subspecies tularensis (type A) is more virulent and predominates in North America; subspecies holarctica (type B) is widespread across Europe and Asia.
Francisella tularensis NCBITaxon:263 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Tularemia caused by Gram-negative, coccobacillus bacterium, Francisella tularensis, is a highly infectious zoonotic disease."
Review identifies F. tularensis as the Gram-negative coccobacillus causative agent of tularemia.
PMID:37916743 SUPPORT Other
"Type A (subspecies tularensis) is more virulent and causes disease mainly in North America; type B (subspecies holarctica) is widespread"
Documents the two principal human-pathogenic subspecies and their geographic distribution and relative virulence.
↔️

Transmission

4
Arthropod bite
Ticks and mosquitoes inoculate F. tularensis through the skin; this is the route behind the ulceroglandular and glandular forms, which are the commonest presentations.
Person-to-person transmission has not been reported for any of these routes (PMID:37916743, "Human-to-human transmission has not been known."), so every route here is an acquisition from an animal, arthropod, or environmental source.
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Vector-borne tularemia primarily involves ticks and mosquitoes."
Names the arthropod vectors that transmit the organism.
PMID:37916743 SUPPORT Other
"Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
Ties the bite route to the clinical forms it produces.
Direct contact with infected animals
Handling infected lagomorphs and rodents, including skinning and dressing game, transmits the organism through skin and conjunctiva. The very low infectious dose makes brief handling sufficient.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"Small mammals like rabbits, hares, and muskrats are primary sources of human infections, but true reservoir of F. tularensis is unknown."
Identifies the small mammals whose handling is the source of human infection.
Ingestion of contaminated food or water
Swallowing contaminated water or undercooked meat from an infected animal produces the oropharyngeal form; water-borne outbreaks are a recurrent pattern in parts of Eurasia.
Show evidence (1 reference)
PMID:37916743 SUPPORT Other
"oro-pharyngeal form by intake of contaminated food or water"
Links ingestion of contaminated food or water to the oropharyngeal form.
Inhalation of infectious aerosols
Inhaled aerosol, whether raised agriculturally from contaminated material or released deliberately, produces pneumonic tularemia. This route and the organism's low infectious dose are why it is a Category A bioterrorism agent.
Show evidence (2 references)
PMID:37916743 SUPPORT Other
"Pulmonary form appears after inhalation of bacteria."
States the inhalational route and the pulmonary form it produces.
PMID:37916743 SUPPORT Other
"F. tularensis is a possible bioweapon due to its lethality, low infectious dosage, and aerosol transmission."
Supports aerosol transmissibility at a low infectious dose as the basis of the bioweapon concern.
📊

Related Datasets

1
Novel transcriptional and translational biomarkers of tularemia vaccine efficacy in a mouse inhalation model: proof of concept geo:GSE186408
Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as small particle aerosols (<5μm). Inhalation of ≥ 20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain that showed efficacy in humans against inhalation of virulent Ftt. However, the breakthrough dose was fairly low and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates.
mouse BULK RNA SEQ n=20
Identified by GEO DataSets index search for Tularemia (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.
{ }

Source YAML

click to show 
name: Tularemia
creation_date: '2026-06-22T00:00:00Z'
category: Infectious Disease
description: >
  Tularemia is a highly infectious zoonotic disease caused by the intracellular
  Gram-negative bacterium Francisella tularensis. Humans acquire infection through
  arthropod (tick or mosquito) bites, direct contact with infected animals
  (especially rabbits, hares, and rodents), ingestion of contaminated food or
  water, or inhalation of infectious aerosols; person-to-person transmission has
  not been reported. After uptake by macrophages, F. tularensis escapes the
  phagosome into the cytosol via the Francisella Pathogenicity Island-encoded type
  VI secretion system, where it replicates and triggers caspase-1 inflammasome
  activation and granulomatous inflammation. The route of inoculation determines
  the clinical form: ulceroglandular, glandular, oculoglandular, oropharyngeal,
  pneumonic, and typhoidal tularemia. F. tularensis requires as few as 10
  organisms to cause disease and is classified as a Category A bioterrorism agent.
disease_term:
  preferred_term: tularemia
  term:
    id: MONDO:0018077
    label: tularemia
parents:
- Bacterial Infection
- Zoonotic Disease
- Tick-Borne Disease
infectious_agent:
- name: Francisella tularensis
  description: >
    Tularemia is caused by the Gram-negative coccobacillus Francisella tularensis.
    Subspecies tularensis (type A) is more virulent and predominates in North
    America; subspecies holarctica (type B) is widespread across Europe and Asia.
  infectious_agent_term:
    preferred_term: Francisella tularensis
    term:
      id: NCBITaxon:263
      label: Francisella tularensis
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Tularemia caused by Gram-negative, coccobacillus bacterium, Francisella tularensis, is a highly infectious zoonotic disease."
    explanation: Review identifies F. tularensis as the Gram-negative coccobacillus causative agent of tularemia.
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Type A (subspecies tularensis) is more virulent and causes disease mainly in North America; type B (subspecies holarctica) is widespread"
    explanation: Documents the two principal human-pathogenic subspecies and their geographic distribution and relative virulence.
has_subtypes:
- name: Glandular form
  display_name: Glandular tularemia
  subtype_term:
    preferred_term: glandular tularemia
    term:
      id: MONDO:0000320
      label: glandular tularemia
  classification: clinical_form
  subtype_frequency: "15.8%"
  description: >-
    Localized tularemia form with acute flu-like symptoms and marked regional
    lymphadenopathy after arthropod or animal inoculation but without the visible
    cutaneous inoculation ulcer that defines the ulceroglandular form.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In glandular form, there are no skin ulcers but lymphadenopathy is marked
    explanation: >-
      The review distinguishes glandular tularemia from ulceroglandular
      tularemia by the absence of a skin ulcer and the presence of marked
      lymphadenopathy.
  - reference: PMID:23104256
    reference_title: Tularemia in central Anatolia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients had clinical presentations compatible with oropharyngeal (74 %),
      glandular (15.8 %), and oculoglandular (5.0 %) tularemia.
    explanation: >-
      This Central Anatolia cohort observed the glandular clinical form in 15.8%
      of confirmed tularemia patients.
- name: Ulceroglandular
  display_name: Ulceroglandular tularemia
  subtype_term:
    preferred_term: ulceroglandular tularemia
    term:
      id: MONDO:0001413
      label: ulceroglandular tularemia
  classification: clinical_form
  description: >-
    Cutaneous-entry form with an inoculation-site ulcer and painful regional
    lymphadenopathy after arthropod bite or infected-animal handling. Curated as
    a standalone entry, Ulceroglandular_Tularemia (MONDO:0001413), which carries
    the cutaneous-inoculation to ulcer-and-regional-node mechanism.
  curated_in: Ulceroglandular_Tularemia
- name: Oculoglandular
  display_name: Oculoglandular tularemia
  subtype_term:
    preferred_term: oculoglandular tularemia
    term:
      id: MONDO:0001665
      label: oculoglandular tularemia
  classification: clinical_form
  subtype_frequency: "5.0%"
  description: >-
    Conjunctival-entry form with granulomatous conjunctivitis and ipsilateral
    preauricular, submandibular, or cervical lymphadenopathy. Curated as a
    standalone entry, Oculoglandular_Tularemia (MONDO:0001665), which carries
    the conjunctival-inoculation to ocular-and-regional-node mechanism.
  curated_in: Oculoglandular_Tularemia
  evidence:
  - reference: PMID:23104256
    reference_title: Tularemia in central Anatolia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients had clinical presentations compatible with oropharyngeal (74 %),
      glandular (15.8 %), and oculoglandular (5.0 %) tularemia.
    explanation: >-
      This Central Anatolia cohort observed the oculoglandular clinical form in
      5.0% of confirmed tularemia patients.
- name: Pneumonic
  display_name: Pneumonic tularemia
  subtype_term:
    preferred_term: pneumonic tularemia
    term:
      id: MONDO:0002212
      label: pneumonic tularemia
  classification: clinical_form
  description: >-
    Inhalational form with pulmonary Francisella tularensis infection and acute
    pneumonic inflammation. Curated as a standalone entry,
    Pneumonic_Tularemia (MONDO:0002212), which carries the aerosol exposure to
    macrophage escape, inflammasome sensing, and inflammatory pneumonia
    mechanism.
  curated_in: Pneumonic_Tularemia
- name: Typhoidal
  display_name: Typhoidal tularemia
  subtype_term:
    preferred_term: typhoidal tularemia
    term:
      id: MONDO:0000321
      label: typhoidal tularemia
  classification: clinical_form
  curated_in: Typhoidal_Tularemia
  subtype_frequency: "14.4%"
  description: >-
    Systemic bacteremic tularemia form without a dominant primary localizing
    lesion; curated as Typhoidal_Tularemia (MONDO:0000321), which carries the
    multisite Francisella-entry route, bacteremic sepsis-like mechanism, and
    typhoidal treatment and diagnostic claims.
  evidence:
  - reference: PMID:40107886
    reference_title: "Tularemia for clinicians: An up-to-date review on epidemiology, diagnosis, prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the multiple routes of infection result in six typical clinical pictures
      (ulceroglandular, glandular, oculoglandular, oropharyngeal, typhoidal, and
      pneumonic)
    explanation: >-
      Identifies typhoidal tularemia as one of the canonical clinical forms that
      result from the multiple Francisella acquisition routes.
  - reference: PMID:24874046
    reference_title: "All-time high tularaemia incidence in Norway in 2011: report from the national surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, oropharyngeal tularaemia (41.1 %) was the most common clinical
      presentation, followed by glandular (14.4 %), typhoidal (14.4 %),
      respiratory (13.3 %) and ulceroglandular (12.8 %) tularaemia.
    explanation: >-
      This high-incidence Norwegian surveillance year observed the typhoidal
      clinical form in 14.4% of tularemia patients.
- name: Gastrointestinal
  display_name: Gastrointestinal tularemia
  subtype_term:
    preferred_term: gastrointestinal tularemia
    term:
      id: MONDO:0001916
      label: gastrointestinal tularemia
  classification: clinical_form
  curated_in: Gastrointestinal_Tularemia
  description: >-
    Enteric form acquired by ingestion of contaminated food or water; curated as
    Gastrointestinal_Tularemia (MONDO:0001916), which carries the ingestion
    portal of entry and the alimentary and draining-node inflammatory mechanism.
  evidence:
  - reference: PMID:19835784
    reference_title: >-
      Effect of dehydrated storage on the survival of Francisella tularensis in
      infant formula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      Francisella tularensis is a Gram-negative bacterium that can cause
      gastrointestinal or oropharyngeal tularemia in humans from ingestion of
      contaminated food or water.
    explanation: >-
      Names gastrointestinal tularemia as a human clinical form of F. tularensis
      infection acquired by ingestion.
transmission:
- name: Arthropod bite
  description: >-
    Ticks and mosquitoes inoculate F. tularensis through the skin; this is the
    route behind the ulceroglandular and glandular forms, which are the commonest
    presentations.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Vector-borne tularemia primarily involves ticks and mosquitoes."
    explanation: Names the arthropod vectors that transmit the organism.
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
    explanation: Ties the bite route to the clinical forms it produces.
  notes: >-
    Person-to-person transmission has not been reported for any of these routes
    (PMID:37916743, "Human-to-human transmission has not been known."), so every
    route here is an acquisition from an animal, arthropod, or environmental source.
- name: Direct contact with infected animals
  description: >-
    Handling infected lagomorphs and rodents, including skinning and dressing game,
    transmits the organism through skin and conjunctiva. The very low infectious
    dose makes brief handling sufficient.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Small mammals like rabbits, hares, and muskrats are primary sources of human infections, but true reservoir of F. tularensis is unknown."
    explanation: Identifies the small mammals whose handling is the source of human infection.
- name: Ingestion of contaminated food or water
  description: >-
    Swallowing contaminated water or undercooked meat from an infected animal
    produces the oropharyngeal form; water-borne outbreaks are a recurrent pattern
    in parts of Eurasia.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "oro-pharyngeal form by intake of contaminated food or water"
    explanation: Links ingestion of contaminated food or water to the oropharyngeal form.
- name: Inhalation of infectious aerosols
  description: >-
    Inhaled aerosol, whether raised agriculturally from contaminated material or
    released deliberately, produces pneumonic tularemia. This route and the
    organism's low infectious dose are why it is a Category A bioterrorism agent.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Pulmonary form appears after inhalation of bacteria."
    explanation: States the inhalational route and the pulmonary form it produces.
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "F. tularensis is a possible bioweapon due to its lethality, low infectious dosage, and aerosol transmission."
    explanation: Supports aerosol transmissibility at a low infectious dose as the basis of the bioweapon concern.
pathophysiology:
- name: Arthropod-Borne and Zoonotic Acquisition
  description: >
    Humans acquire F. tularensis through arthropod bites (ticks and mosquitoes),
    handling of infected animals, ingestion of contaminated food or water, or
    inhalation of contaminated aerosols. The route of entry determines the
    resulting clinical form.
  biological_processes:
  - preferred_term: Phagocytosis
    term:
      id: GO:0006909
      label: phagocytosis
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals, oculo-glandular form as a result of conjunctival infection, and oro-pharyngeal form by intake of contaminated food or water."
    explanation: Establishes that the route of inoculation determines the clinical form of tularemia.
  - reference: PMID:37941380
    reference_title: "Pathogenicity and virulence of Francisella tularensis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Depending on its entry route into the organism, F. tularensis causes different diseases, ranging from life-threatening pneumonia to less severe ulceroglandular tularaemia."
    explanation: Confirms entry route determines disease severity and clinical form.
  downstream:
  - target: Macrophage Phagosomal Escape and Cytosolic Replication
    description: >
      Following inoculation, F. tularensis is taken up by macrophages, where it
      establishes its intracellular replicative niche.
    causal_link_type: DIRECT
- name: Macrophage Phagosomal Escape and Cytosolic Replication
  description: >
    F. tularensis enters macrophages by looping phagocytosis. The
    Francisella-containing phagosome matures transiently before the bacterium
    escapes into the cytosol within 30-60 minutes via the Francisella
    Pathogenicity Island-encoded type VI secretion system (T6SS), then proliferates
    in the cytosol. The T6SS and its effectors are the main virulence attribute
    promoting phagosomal escape.
  cell_types:
  - preferred_term: Macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: Suppression of host phagosome maturation
    term:
      id: GO:0141158
      label: symbiont-mediated suppression of host phagosome maturation
  - preferred_term: Symbiont entry into host
    term:
      id: GO:0044409
      label: symbiont entry into host
  evidence:
  - reference: PMID:37941380
    reference_title: "Pathogenicity and virulence of Francisella tularensis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The main virulence attribute of F. tularensis is the type 6 secretion system (T6SS) and its effectors that promote escape from the phagosome."
    explanation: Identifies the FPI-encoded T6SS as the principal virulence factor mediating phagosomal escape.
  - reference: PMID:19863554
    reference_title: "Cell biology and molecular ecology of Francisella tularensis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Entry of F. tularensis into macrophages is mediated by looping phagocytosis"
    explanation: Describes the looping phagocytosis mechanism of macrophage entry.
  - reference: PMID:19863554
    reference_title: "Cell biology and molecular ecology of Francisella tularensis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The Francisella pathogenicity island, which potentially encodes a putative type VI secretion system, is essential for phagosome biogenesis and bacterial escape into the cytosol within macrophages and arthropod-derived cells."
    explanation: Confirms the FPI/T6SS is essential for bacterial escape into the macrophage cytosol.
  downstream:
  - target: Inflammasome Activation and Granulomatous Inflammation
    description: >
      Cytosolic replication of F. tularensis is sensed by the host innate immune
      system, triggering caspase-1 inflammasome activation and a pro-inflammatory,
      granulomatous response.
    causal_link_type: DIRECT
  - target: Lymphatic Francisella Spread to Regional Nodes
    description: >
      Organisms introduced through skin or mucosa can drain from the inoculation
      territory into the regional lymph node basin.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Lymphatic Francisella Spread to Regional Nodes
  description: >-
    After peripheral inoculation, F. tularensis drains through lymphatics into
    the regional node basin, anatomically localizing glandular and
    ulceroglandular tularemia as painful regional lymphadenitis.
  locations:
  - preferred_term: lymph node
    term:
      id: UBERON:0000029
      label: lymph node
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37941380
    reference_title: "Pathogenicity and virulence of Francisella tularensis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Later, one or more chronically evolving lymphadenopathies can develop in
      the lymphatic system draining the site of entry.
    explanation: >-
      The Francisella review connects the portal of entry to later
      lymphadenopathy in the draining lymphatic basin.
  downstream:
  - target: Necrotizing and Suppurative Granulomatous Lymphadenitis
    description: >-
      Node infection drives granulomatous and suppurative tissue inflammation.
    causal_link_type: DIRECT
- name: Necrotizing and Suppurative Granulomatous Lymphadenitis
  description: >-
    Node-localized tularemia produces granulomas, necrosis, abscess-forming
    suppuration, and extracapsular inflammation; fluctuant infected nodes can
    require fine-needle aspiration, drainage, or excision.
  locations:
  - preferred_term: lymph node
    term:
      id: UBERON:0000029
      label: lymph node
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:23763361
    reference_title: "Tularemia: potential role of cytopathology in differential diagnosis of cervical lymphadenitis: multicenter experience in 53 cases and literature review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On histopathology; granulomas, necrosis, and suppurative inflammation
      extending extracapsular areas were seen.
    explanation: >-
      Human node cytology and resection specimens establish granulomatous,
      necrotizing, suppurative lymphadenitis as a tularemia tissue pattern.
  downstream:
  - target: Lymphadenopathy
    description: >-
      Granulomatous and suppurative node inflammation produces painful regional
      lymph node enlargement.
    causal_link_type: DIRECT
- name: Inflammasome Activation and Granulomatous Inflammation
  description: >
    Cytosolic sensing of F. tularensis triggers IRF-3-dependent IFN-beta secretion
    and activation of the caspase-1 inflammasome with a pro-inflammatory response.
    The resulting inflammation produces granulomatous lesions and the systemic and
    localized clinical manifestations of tularemia, including fever, regional
    lymphadenopathy, skin ulceration, and pneumonia.
  cell_types:
  - preferred_term: Macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: Inflammasome-mediated signaling
    term:
      id: GO:0141084
      label: inflammasome-mediated signaling pathway
  - preferred_term: Inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:19863554
    reference_title: "Cell biology and molecular ecology of Francisella tularensis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "activation of the inflammasome mediated by caspase-1, and a pro-inflammatory response"
    explanation: Establishes caspase-1 inflammasome activation and a pro-inflammatory response as the host innate response to cytosolic F. tularensis.
  downstream:
  - target: Fever
    description: Systemic inflammation produces fever, the most consistent finding across tularemia forms.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Headache
    description: Systemic inflammation contributes to headache in the flu-like prodrome.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Myalgia
    description: Systemic inflammation contributes to myalgia in the flu-like prodrome.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Lymphadenopathy
    description: Regional inflammation produces lymph node enlargement, the hallmark of glandular and ulceroglandular forms.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Skin Ulcer
    description: Inflammation at a cutaneous inoculation site produces the ulcer of ulceroglandular tularemia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Pneumonia
    description: Inflammation following inhalational exposure produces pneumonic tularemia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Chills
    description: Systemic inflammatory cytokines drive the chills of the early flu-like phase.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Francisella Ribosomal Translation
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  description: >-
    Francisella depends on bacterial 70S ribosomal translation for protein
    synthesis; aminoglycosides and tetracyclines used for tularemia act on this
    conserved bacterial ribosomal target.
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:24336183
    reference_title: "Ribosome-targeting antibiotics and mechanisms of bacterial resistance."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The ribosome is one of the main antibiotic targets in the bacterial cell.
    explanation: >-
      Review support for the shared bacterial-ribosome target of
      aminoglycosides and tetracyclines.
  downstream: []
- name: Francisella DNA Gyrase and Topoisomerase IV
  role: therapeutic_vulnerability
  conforms_to: "bacterial_dna_topoisomerase_inhibition#DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)"
  description: >-
    F. tularensis requires bacterial type II topoisomerases to control DNA
    supercoiling and chromosome segregation; fluoroquinolones used for tularemia
    trap gyrase/topoisomerase-DNA cleavage complexes at this druggable target.
  biological_processes:
  - preferred_term: DNA topological change
    term:
      id: GO:0006265
      label: DNA topological change
  evidence:
  - reference: PMID:27449972
    reference_title: "Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Quinolones dually target DNA gyrase and topoisomerase IV binding to
      specific domains and conformations so as to block DNA strand passage
      catalysis and stabilize DNA-enzyme complexes that block the DNA
      replication apparatus and generate double breaks in DNA that underlie
      their bactericidal activity.
    explanation: >-
      Review support for the bacterial DNA gyrase/topoisomerase IV target of
      fluoroquinolones.
  downstream: []
phenotypes:
- name: Fever
  description: >
    Fever is the most consistent clinical feature of tularemia and is present in
    most cases regardless of clinical form, typically as part of an early flu-like
    illness.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia that may or may not include lymphadenopathy."
    explanation: Review describes the early flu-like (febrile) presentation of tularemia preceding localized findings.
- name: Lymphadenopathy
  subtypes:
  - Glandular form
  description: >
    Regional lymphadenopathy is the hallmark of the glandular and ulceroglandular
    forms, draining the site of inoculation.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
    explanation: Glandular and ulceroglandular forms are defined by regional lymphadenopathy following arthropod or animal exposure.
  - reference: PMID:38294108
    reference_title: "Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease."
    explanation: CDC systematic review of 870 human cases confirms glandular and ulceroglandular (lymphadenopathy-defined) forms are among the most common.
- name: Skin Ulcer
  notes: >-
    This finding defines the ulceroglandular form and is absent by definition in
    the MONDO:0000320 glandular form.
  description: >
    A skin ulcer at the cutaneous site of inoculation is the defining lesion of
    ulceroglandular tularemia, the most common clinical form.
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals"
    explanation: The ulceroglandular form is characterized by a skin ulcer at the inoculation site.
- name: Pneumonia
  description: >
    Pneumonic tularemia follows inhalation of infectious aerosols and is among the
    most severe and most common clinical forms; it can also arise secondarily by
    hematogenous spread.
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Pulmonary form appears after inhalation of bacteria."
    explanation: The pulmonary (pneumonic) form of tularemia follows inhalational exposure.
  - reference: PMID:38294108
    reference_title: "Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease."
    explanation: CDC systematic review confirms pneumonic disease is among the most common clinical forms of human tularemia.
- name: Chills
  description: Chills accompany the early febrile, flu-like phase of tularemia.
  phenotype_term:
    preferred_term: Chills
    term:
      id: HP:0025143
      label: Chills
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia"
    explanation: The early flu-like illness of tularemia includes constitutional symptoms such as chills.
- name: Headache
  description: Headache is part of the early influenza-like tularemia prodrome.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:37941380
    reference_title: "Pathogenicity and virulence of Francisella tularensis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      At onset, tularaemia symptoms are non-specific and include a flu-like
      syndrome with fever, headache, muscle and joint aches (myalgia, and/or
      arthralgia).
    explanation: >-
      Review evidence that headache is part of the early nonspecific
      influenza-like tularemia syndrome.
- name: Myalgia
  description: Myalgia is part of the early influenza-like tularemia prodrome.
  phenotype_term:
    preferred_term: Myalgia
    term:
      id: HP:0003326
      label: Myalgia
  evidence:
  - reference: PMID:37941380
    reference_title: "Pathogenicity and virulence of Francisella tularensis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      At onset, tularaemia symptoms are non-specific and include a flu-like
      syndrome with fever, headache, muscle and joint aches (myalgia, and/or
      arthralgia).
    explanation: >-
      Review evidence that myalgia is part of the early nonspecific
      influenza-like tularemia syndrome.
treatments:
- name: Streptomycin
  description: >
    Aminoglycoside, historically the first-line agent for tularemia. In a CDC
    systematic review of human cases, aminoglycosides were associated with a low
    fatality rate (0.7%).
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: streptomycin
      term:
        id: CHEBI:17076
        label: streptomycin
  target_mechanisms:
  - target: Francisella Ribosomal Translation
    treatment_effect: INHIBITS
    description: >-
      Streptomycin is an aminoglycoside that treats tularemia by acting at the
      bacterial ribosome.
  evidence:
  - reference: PMID:38294108
    reference_title: "Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation."
    explanation: CDC systematic review confirms aminoglycosides (e.g., streptomycin) are effective for tularemia.
- name: Ciprofloxacin
  description: >
    Fluoroquinolone used for tularemia. In the CDC systematic review, patients
    with pneumonic disease who received ciprofloxacin had no fatalities and the
    lowest rates of complications.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ciprofloxacin
      term:
        id: CHEBI:100241
        label: ciprofloxacin
  target_mechanisms:
  - target: Francisella DNA Gyrase and Topoisomerase IV
    treatment_effect: INHIBITS
    description: >-
      Ciprofloxacin is a fluoroquinolone that treats tularemia through the
      conserved bacterial type-II-topoisomerase target.
  evidence:
  - reference: PMID:38294108
    reference_title: "Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials."
    explanation: CDC systematic review notes ciprofloxacin may have advantages for pneumonic tularemia.
- name: Doxycycline
  description: >
    Tetracycline-class agent used for tularemia. Tetracyclines were associated
    with effective treatment across clinical forms but with higher relapse rates
    than bactericidal agents.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
  target_mechanisms:
  - target: Francisella Ribosomal Translation
    treatment_effect: INHIBITS
    description: >-
      Doxycycline is a tetracycline that treats tularemia by acting at the
      bacterial ribosome.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Treatment for tularemia typically entails use of quinolones, tetracyclines, or aminoglycosides."
    explanation: Review lists tetracyclines (e.g., doxycycline) among the standard antimicrobial classes for tularemia.
- name: Fine-Needle Aspiration or Surgical Drainage
  description: >-
    Fluctuant or necrotic tularemia lymph nodes may require fine-needle
    aspiration, surgical drainage, or excision as adjunctive source control.
  therapeutic_modality: SURGERY
  target_mechanisms:
  - target: Necrotizing and Suppurative Granulomatous Lymphadenitis
    description: >-
      Needle aspiration, drainage, and excision remove the suppurative lymph-node
      compartment responsible for persistent regional disease.
  evidence:
  - reference: PMID:23104256
    reference_title: Tularemia in central Anatolia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fine-needle aspiration (FNA) or surgical drainage of fluctuant lymph nodes
      were performed in 51 (39 %) patients.
    explanation: >-
      The prospective Central Anatolia series documents node aspiration or
      drainage in 39% of confirmed tularemia cases with fluctuant nodes.
diagnosis:
- name: Serology or Microagglutination Testing
  diagnosis_term:
    preferred_term: Diagnostic serology and microagglutination testing
    term:
      id: NCIT:C217458
      label: Diagnostic Serology Testing
  measurements:
  - preferred_term: Francisella tularensis antibody serology
    term:
      id: LOINC:93715-1
      label: Francisella tularensis IgG and IgM panel - Serum
  description: >-
    Tularemia is commonly confirmed serologically by a positive
    microagglutination test or by seroconversion on paired sera when the first
    sample is negative early in the course. Serology should be considered when a
    cervical lymphadenitis syndrome fails beta-lactam treatment, because delayed
    appropriate therapy is associated with poorer outcomes.
  evidence:
  - reference: PMID:22090310
    reference_title: "[Evaluation of tularemia cases originated from Central Anatolia, Turkey]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      with fever, sore throat, cervical mass and failure to respond to
      beta-lactam antibiotics, were followed up with the preliminary diagnosis
      of tularemia.
    explanation: >-
      Central Anatolia clinicians escalated cervical lymphadenitis cases with
      beta-lactam nonresponse to suspected tularemia, supporting the diagnostic
      implication of intrinsic beta-lactam resistance.
  - reference: PMID:22090310
    reference_title: "[Evaluation of tularemia cases originated from Central Anatolia, Turkey]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The patients who applied to the hospital within 10 days of the initiation
      of the symptoms were treated successfully, while the others that applied
      later were not.
    explanation: >-
      The same case series links early presentation with successful treatment,
      supporting diagnostic delay as a modifiable driver of morbidity.
  - reference: PMID:22090310
    reference_title: "[Evaluation of tularemia cases originated from Central Anatolia, Turkey]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All of the 8 patients who had negative results in their first samples (<
      1/160), revealed seroconversion in their second samples.
    explanation: >-
      The outbreak case series illustrates paired-serum microagglutination
      diagnosis, including later seroconversion after initially negative tests.
- name: Francisella PCR on Lesional or Node Specimens
  diagnosis_term:
    preferred_term: Francisella PCR on lesional or node specimens
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  description: >-
    PCR detection of F. tularensis DNA in wound or lymph-node material can
    confirm tularemia before seroconversion and can outperform culture, which is
    insensitive and hazardous for laboratories.
  evidence:
  - reference: PMID:10618057
    reference_title: Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of 40 patients with culture- and/or serology-verified ulceroglandular
      tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas
      culture detected bacterial growth in 25 (62%) patients.
    explanation: >-
      Direct comparison in human ulceroglandular tularemia supports PCR as a
      more sensitive direct detection method than culture.
- name: Lymph-Node Fine-Needle Aspiration and Histopathology
  diagnosis_term:
    preferred_term: Lymph-node fine-needle aspiration and histopathology
    term:
      id: NCIT:C15361
      label: Fine-Needle Aspiration
  description: >-
    Fine-needle aspiration of cervical nodes can show suppurative,
    granulomatous lymphadenitis and provide material for PCR or culture.
  evidence:
  - reference: PMID:23763361
    reference_title: "Tularemia: potential role of cytopathology in differential diagnosis of cervical lymphadenitis: multicenter experience in 53 cases and literature review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      However FNA cytology is helpful in differential diagnosis of tularemia and
      other diseases presented with suppurative, granulomatous cervical
      lymphadenitis.
    explanation: >-
      Multicenter experience with 53 aspirates supports FNA cytology as a
      differential-diagnostic test for suppurative granulomatous tularemia
      lymphadenitis.
environmental:
- name: Arthropod and infected-animal contact
  description: >-
    Tick, mosquito, and other arthropod bites or direct handling of infected
    animals are exposure routes that can inoculate F. tularensis into skin and
    soft tissue, triggering ulceroglandular or glandular tularemia.
  effect: Increases risk of localized arthropod-borne or animal-contact tularemia.
  influences_mechanisms:
  - target: Arthropod-Borne and Zoonotic Acquisition
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Arthropod or animal contact introduces F. tularensis at the portal of
      entry, initiating the macrophage infection chain.
    evidence:
    - reference: PMID:37916743
      reference_title: "Tularemia - a re-emerging disease with growing concern."
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Ulcero-glandular and glandular forms are acquired by arthropod bite or
        handling of infected animals
      explanation: >-
        The review identifies arthropod bite and infected-animal handling as
        acquisition routes for the glandular and ulceroglandular forms.
  evidence:
  - reference: PMID:37916743
    reference_title: "Tularemia - a re-emerging disease with growing concern."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Ulcero-glandular and glandular forms are acquired by arthropod bite or
      handling of infected animals
    explanation: >-
      The review identifies the external exposures that lead to the localized
      glandular and ulceroglandular forms.
epidemiology:
- name: Regional seroprevalence (WHO-EMRO)
  description: >
    Tularemia is endemic across the Northern Hemisphere and is re-emerging in many
    countries. A 2024 systematic review and meta-analysis of the WHO Eastern
    Mediterranean Region estimated a human seroprevalence of 6.2%, with the
    pathogen also detected in environmental samples, ticks, rodents, and domestic
    ruminants.
  evidence:
  - reference: PMID:38728365
    reference_title: "Epidemiology of tularemia in the countries of the WHO Eastern Mediterranean Region (EMRO): A systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The human seroprevalence of tularemia in WHO-EMRO countries was 6.2%"
    explanation: Meta-analysis quantifies regional human seroprevalence of tularemia.
references:
- reference: PMID:37941380
  title: "Pathogenicity and virulence of Francisella tularensis."
- reference: PMID:38294108
  title: "Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023."
datasets:
- accession: geo:GSE186408
  title: 'Novel transcriptional and translational biomarkers of tularemia vaccine efficacy in a mouse inhalation model: proof of concept'
  description: Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as small particle aerosols (<5μm). Inhalation of ≥ 20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain that showed efficacy in humans against inhalation of virulent Ftt. However, the breakthrough dose was fairly low and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 20
  notes: Identified by GEO DataSets index search for Tularemia (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.
📚

References & Deep Research

References

2
PMID:37941380
Pathogenicity and virulence of Francisella tularensis.
No top-level findings curated for this source.
PMID:38294108
Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023.
No top-level findings curated for this source.

Deep Research

1

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

Evaluations and curation notes (1)

Add: Glandular Tularemia subtype · 2026-09-27T01:31:33Z · View source

Responded to PR #12814 review by replacing the standalone Glandular_Tularemia entry with a MONDO:0000320 clinical subtype inside Tularemia. Preserved the OpenScientist deep-research report, moved form-specific regional-node curation into the parent entry, added lymphatic spread and necrotizing/suppurative granulomatous lymphadenitis nodes, added headache and myalgia prodromal phenotypes, added serology, PCR, and FNA/histopathology diagnostics, linked arthropod and infected-animal exposure into the pathograph, and connected tularemia antibiotics to ribosomal or topoisomerase target mechanisms plus drainage/excision to suppurative lymphadenitis. Validated Tularemia with schema, term, title, exact-snippet, causal-target, entity-reference, and duplicate-key checks before creating this record.

Falcon ▸
1. Disease Information / Identifiers
Edison Scientific Literature 26 citations 2026-06-22T12:06:36.534153

1. Disease Information / Identifiers

Tularemia is a highly infectious zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. It is recognized under multiple disease coding systems. While explicit codes from OMIM, Orphanet, MeSH, and MONDO were not directly recoverable in the available evidence, the ICD-10 code for tularemia is A21. Recognized synonyms include: tularemia, tularaemia, rabbit fever, deer fly fever, wild hare disease, Ohara’s disease, and water-rat trappers’ disease. Detailed mapping and methodology are maintained by Mondo and Orphanet for improved terminological interoperability, as summarized below:

Resource Code Preferred label Synonyms URL/reference
OMIM Not established / no disease-specific OMIM code confidently confirmed from available context Tularemia Rabbit fever; deer fly fever; water-rat trappers’ disease; wild hare disease; Ohara’s disease (literature synonyms) (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2) OMIM is one of the external terminologies integrated by Mondo and mapped by Orphanet in general, but the tularemia-specific OMIM identifier was not recoverable from the available context excerpts without risking overstatement (vasilevsky2022mondounifyingdiseases pages 4-6, lucano2025theorphanetnomenclature pages 12-15, lucano2025theorphanetnomenclature pages 15-19). General OMIM: https://www.omim.org
Orphanet ORPHAcode present in Orphanet alignments, but tularemia-specific code not recoverable from available context excerpts Tularemia Rabbit fever; tularaemia/tularemia; deer fly fever; Ohara’s disease; wild hare disease; water-rat trappers’ disease (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2) Orphanet maintains rare-disease identifiers and maps them to ICD-10, ICD-11, OMIM, MeSH, and MONDO; infectious rare diseases are included in Orphanet’s scope in Europe (lucano2025theorphanetnomenclature pages 12-15, lucano2025theorphanetnomenclature pages 15-19, lucano2025theorphanetnomenclature pages 26-29). General Orphanet: http://www.orpha.net/
ICD-10 A21 Tularemia Rabbit fever; tularaemia/tularemia (literature/terminology consensus) (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2) Orphanet reports broad ICD-10 coverage and mapping procedures for rare diseases; tularemia is the standard ICD-10 entity A21. General ICD-10 reference framework discussed in Orphanet nomenclature papers (lucano2025theorphanetnomenclature pages 15-19, lucano2025theorphanetnomenclature pages 26-29). WHO ICD resources: https://icd.who.int
MeSH MeSH term exists for Tularemia, but exact descriptor ID not recoverable from available context excerpts Tularemia Rabbit fever; tularaemia/tularemia (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2) MeSH is explicitly listed by Orphanet as a mapped target terminology and cited by Mondo as a major disease vocabulary resource, but the tularemia-specific MeSH identifier was not present in the available excerpts (lucano2025theorphanetnomenclature pages 12-15, vasilevsky2022mondounifyingdiseases pages 11-12). General MeSH: https://www.ncbi.nlm.nih.gov/mesh
MONDO MONDO term exists in principle for infectious diseases including tularemia, but tularemia-specific MONDO ID not recoverable from available context excerpts Tularemia Rabbit fever; tularaemia/tularemia; deer fly fever; Ohara’s disease; wild hare disease; water-rat trappers’ disease (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2) Mondo integrates OMIM, ICD-10-CM, Orphanet, MeSH-linked sources, and infectious diseases with stable MONDO identifiers and scoped synonyms; however, the tularemia-specific MONDO accession was not contained in the available text snippets (vasilevsky2022mondounifyingdiseases pages 4-6, vasilevsky2022mondounifyingdiseases pages 6-11). General Mondo: https://mondo.monarchinitiative.org/

Table: This table summarizes Tularemia identifiers and preferred naming across major disease vocabularies using only information supportable from the available context. It is useful as a cautious crosswalk because it distinguishes confirmed terminology relationships from identifiers that were not directly recoverable in the provided source excerpts.

2. Etiology, Transmission, and Risk Factors

Tularemia is a zoonosis caused by F. tularensis, which infects a wide range of mammals (especially lagomorphs and rodents), birds, amphibians, invertebrates, and humans. The disease is re-emerging in many countries, and is recognized as a Category A biothreat agent due to its high infectivity and diverse transmission routes. Tularemia is primarily acquired via: - Direct contact with infected wild animals (especially rabbits, hares, voles, water voles). - Arthropod vectors: Predominantly ticks (Dermacentor, Ixodes) and mosquitoes in northern Europe and North America, with some regional specificity (e.g., Aedes cinereus in Sweden). - Ingestion of contaminated water, food, or contact with contaminated environments (aquatic/soil biofilms). - Inhalation of infectious aerosols or dust. Transmission is typically from the environment and animals—human-to-human transmission is not reported. F. tularensis is environmentally resilient, surviving for prolonged periods in water and soil. The most recent regional meta-analysis estimated human seroprevalence in the WHO Eastern Mediterranean region at 6.2% (95% CI: 4.2–9.2). Environmental prevalence (water/soil) was 5.8%; ticks showed 2.5% positivity, rodents 2.0%, and domestic ruminants 0.6% (sholeh2024epidemiologyoftularemia pages 1-2). Risk factors are predominantly environmental (outdoor activities, wildlife exposure) and occupational (e.g., farmers, hunters, laboratory workers). "Prophylactic measures must be adapted in each tularemia endemic area according to the predominant modes of human and animal infection. They require a One Health approach to control both animal and environmental reservoirs... as well as arthropod vectors, to slow the current expansion of endemic areas of this disease in a context of climate change" (maurin2024nonvaccinalprophylaxisof pages 1-2).

“Tularemia is a re-emerging zoonosis in many endemic countries. It is caused by Francisella tularensis, a gram-negative bacterium and biological threat agent.” Humans acquire infection “from the wild animal reservoir, the environmental reservoir or by the bite of arthropod vectors,” via “cutaneous, conjunctival, digestive or respiratory routes” (maurin2024nonvaccinalprophylaxisof pages 1-2).

Recent reviews agree that the causal agent is primarily F. tularensis subsp. tularensis (type A, more virulent, mainly North America) and subsp. holarctica (type B, widespread across Europe/Asia), while subsp. mediasiatica has not been isolated from human cases in the cited summaries (sholeh2024epidemiologyoftularemia pages 1-2, sharma2023tularemia–a pages 2-3).

Key transmission routes in current understanding are direct contact with infected animals, arthropod bites, inhalation of contaminated aerosols/dust, and ingestion of contaminated food or water. The 2024 EMRO meta-analysis states that F. tularensis is transferred to humans through “contact with infected wild animals,” “inhalation of infected aerosols,” “arthropod bites,” and “consumption of contaminated water or contaminated food” (sholeh2024epidemiologyoftularemia pages 1-2).

Important animal and vector risk factors include lagomorph and rodent exposure, especially rabbits, hares, voles, and water voles; ticks and mosquitoes are the dominant vectors in most endemic settings. The 2023 review notes that “ticks act as both reservoirs as well as vectors of infection since they can carry the bacteria by transstadial as well as transovarial transmission,” and that in Sweden and Finland “most of the cases of tularemia occur by the bite of mosquitoes” (sharma2023tularemia–a pages 2-3).

Environmental persistence is now emphasized as part of the zoonotic cycle: F. tularensis “can survive for prolonged periods in aquatic and soil environments,” and tularemia risk is shaped by wildlife reservoirs plus environmental reservoirs, not only animal contact alone (maurin2024nonvaccinalprophylaxisof pages 1-2).

Illustrative recent epidemiologic data from the 2024 WHO-EMRO systematic review/meta-analysis show measurable exposure across humans, vectors, reservoirs, and environment: human seroprevalence 6.2% (95% CI 4.2–9.2), high-risk individuals 6.92%, environmental samples 5.8% overall (9.4% by PCR; 0.5% by culture), ticks 2.5%, rodents 2.0%, and domestic ruminants 0.6% (sholeh2024epidemiologyoftularemia pages 1-2).

These data support a multi-compartment risk model: human risk rises where infected wildlife, vectors, and contaminated water/soil overlap. The same meta-analysis concludes that tularemia is “an endemic but neglected disease” in the WHO-EMRO region, underscoring under-recognition outside classic hotspots (sholeh2024epidemiologyoftularemia pages 1-2).

Geographic and ecological risk is heterogeneous. The 2023 review highlights that Europe has seen re-emergence, including “a four-fold increase in Switzerland and a 10-fold increase in Sweden in the last three decades,” with Scandinavia reporting particularly high annual case numbers; type A remains largely restricted to North America, whereas type B predominates in Europe and Asia (sharma2023tularemia–a pages 2-3).

Protective factors are mostly environmental and behavioral rather than genetic in the current literature excerpts: avoiding arthropod bites, limiting exposure to potentially infected wildlife/carcasses, reducing inhalation of contaminated dust during outdoor/agricultural activities, and preventing use of contaminated water sources are the main implied protective measures; no validated human protective genetic variants were identified in the available 2023–2024 context (sholeh2024epidemiologyoftularemia pages 1-2, maurin2024nonvaccinalprophylaxisof pages 1-2).

Expert opinion in 2024 strongly favors a One Health framework: “Prophylactic measures must be adapted in each tularemia endemic area according to the predominant modes of human and animal infection. They requires a One Health approach to control both animal and environmental reservoirs of F. tularensis, as well as arthropod vectors, to slow the current expansion of endemic areas of this disease in a context of climate change” (maurin2024nonvaccinalprophylaxisof pages 1-2).

Blockquote: This blockquote summarizes 2023-2024 evidence on tularemia causation, transmission routes, reservoir/vector ecology, risk factors, and prevention-relevant One Health insights. It includes direct quotes and recent pooled statistics useful for a disease knowledge base entry.

No validated human genetic risk or protective variants were reported in recent authoritative reviews (2023–2024). Protective factors are behavioral and environmental (preventing tick/mosquito bites, avoiding contact with wildlife, using safe water sources).

3. Phenotypes and Clinical Spectrum (Partial)

While a complete recent phenotypic breakdown could not be synthesized before the time expiration, tularemia displays a diverse clinical picture determined largely by the infection route: - Ulceroglandular form: most common, following arthropod bites or animal contact—characterized by skin ulcer at entry site with regional lymphadenopathy. - Glandular form: regional lymphadenopathy without skin ulceration. - Oculoglandular, oropharyngeal, pulmonary, and typhoidal forms: related to local entry and systemic involvement; severe cases may progress to pneumonia, sepsis, or typhoidal illness. - General symptoms: high fever, fatigue, malaise, and flu-like illness precede localized findings.

Complications can include pneumonia, sepsis, myocarditis, and chronic symptoms if untreated. No established HPO term mapping was extracted in this time-constrained run.

4. Genetic and Molecular Information

Tularemia is not a genetic or hereditary disease. There are no confirmed causal genes, chromosomal abnormalities, or pathogenic variants in humans. All cases are related to infection by F. tularensis (sharma2023tularemia–a pages 1-2, degabriel2023pathogenicityandvirulence pages 1-2, sholeh2024epidemiologyoftularemia pages 1-2).

5. Environmental Information

Tularemia is intimately linked to environmental exposures, with aquatic, soil, and animal reservoirs all contributing to persistence and outbreaks. The pathogen is resilient and adapts to biofilm and environmental niches, made more significant by climate and ecological changes (maurin2024nonvaccinalprophylaxisof pages 1-2).

References / URLs (Cited Contexts)

  • Maurin M, Hennebique A, Brunet C, et al. Non-vaccinal prophylaxis of tularemia. Front Microbiol. 2024. https://doi.org/10.3389/fmicb.2024.1507469 (maurin2024nonvaccinalprophylaxisof pages 1-2)
  • Sholeh M, Moradkasani S, Esmaeili S. Epidemiology of tularemia in the countries of the WHO Eastern Mediterranean Region (EMRO): A systematic review and meta-analysis. PLoS Negl Trop Dis. 2024. https://doi.org/10.1371/journal.pntd.0012141 (sholeh2024epidemiologyoftularemia pages 1-2)
  • Sharma R, Patil RD, Singh B, et al. Tularemia – a re-emerging disease with growing concern. Veterinary Quarterly. 2023. https://doi.org/10.1080/01652176.2023.2277753 (sharma2023tularemia–a pages 1-2, sharma2023tularemia–a pages 2-3)

Further detailed clinical, diagnostic, prognostic, and treatment characteristics require continued evidence synthesis, as multiple high-value targets remain in the plan.

References

  1. (sharma2023tularemia–a pages 1-2): Rinku Sharma, Rajendra Damu Patil, Birbal Singh, Sandip Chakraborty, Deepak Chandran, Kuldeep Dhama, Devi Gopinath, Gauri Jairath, Ajayta Rialch, Gorakh Mal, Putan Singh, Wanpen Chaicumpa, and G. Saikumar. Tularemia – a re-emerging disease with growing concern. Veterinary Quarterly, 43:1-16, Nov 2023. URL: https://doi.org/10.1080/01652176.2023.2277753, doi:10.1080/01652176.2023.2277753. This article has 48 citations and is from a domain leading peer-reviewed journal.

  2. (degabriel2023pathogenicityandvirulence pages 1-2): Manon Degabriel, Stanimira Valeva, Sandrine Boisset, and Thomas Henry. Pathogenicity and virulence of francisella tularensis. Virulence, Nov 2023. URL: https://doi.org/10.1080/21505594.2023.2274638, doi:10.1080/21505594.2023.2274638. This article has 49 citations and is from a peer-reviewed journal.

  3. (vasilevsky2022mondounifyingdiseases pages 4-6): Nicole A Vasilevsky, Nicolas A Matentzoglu, Sabrina Toro, Joseph E Flack, Harshad Hegde, Deepak R Unni, Gioconda F Alyea, Joanna S Amberger, Larry Babb, James P Balhoff, Taylor I Bingaman, Gully A Burns, Orion J Buske, Tiffany J Callahan, Leigh C Carmody, Paula Carrio Cordo, Lauren E Chan, George S Chang, Sean L Christiaens, Michel Dumontier, Laura E Failla, May J Flowers, H. Alpha Garrett, Jennifer L Goldstein, Dylan Gration, Tudor Groza, Marc Hanauer, Nomi L Harris, Jason A Hilton, Daniel S Himmelstein, Charles Tapley Hoyt, Megan S Kane, Sebastian Köhler, David Lagorce, Abbe Lai, Martin Larralde, Antonia Lock, Irene López Santiago, Donna R Maglott, Adriana J Malheiro, Birgit H M Meldal, Monica C Munoz-Torres, Tristan H Nelson, Frank W Nicholas, David Ochoa, Daniel P Olson, Tudor I Oprea, David Osumi-Sutherland, Helen Parkinson, Zoë May Pendlington, Ana Rath, Heidi L Rehm, Lyubov Remennik, Erin R Riggs, Paola Roncaglia, Justyne E Ross, Marion F Shadbolt, Kent A Shefchek, Morgan N Similuk, Nicholas Sioutos, Damian Smedley, Rachel Sparks, Ray Stefancsik, Ralf Stephan, Andrea L Storm, Doron Stupp, Gregory S Stupp, Jagadish Chandrabose Sundaramurthi, Imke Tammen, Darin Tay, Courtney L Thaxton, Eloise Valasek, Jordi Valls-Margarit, Alex H Wagner, Danielle Welter, Patricia L Whetzel, Lori L Whiteman, Valerie Wood, Colleen H Xu, Andreas Zankl, Xingmin Aaron Zhang, Christopher G Chute, Peter N Robinson, Christopher J Mungall, Ada Hamosh, and Melissa A Haendel. Mondo: unifying diseases for the world, by the world. MedRxiv, Apr 2022. URL: https://doi.org/10.1101/2022.04.13.22273750, doi:10.1101/2022.04.13.22273750. This article has 158 citations.

  4. (lucano2025theorphanetnomenclature pages 12-15): C. Lucano, D. Lagorce, A. Olry, H. Ali, V. Lanneau, M. De Carvalho, A. Dilsizoglu Senol, M. Fructuoso, E. Gaillard, M.-C. Gaillard, S. Mihic, M. Tannoury, F. Sauvage, C. Rodwell, S. Maiella, M. Hanauer, and A. Rath. The orphanet nomenclature of rare diseases: a standard terminology for improved patient recognition and data interoperability. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.10.25333394, doi:10.1101/2025.08.10.25333394. This article has 3 citations.

  5. (lucano2025theorphanetnomenclature pages 15-19): C. Lucano, D. Lagorce, A. Olry, H. Ali, V. Lanneau, M. De Carvalho, A. Dilsizoglu Senol, M. Fructuoso, E. Gaillard, M.-C. Gaillard, S. Mihic, M. Tannoury, F. Sauvage, C. Rodwell, S. Maiella, M. Hanauer, and A. Rath. The orphanet nomenclature of rare diseases: a standard terminology for improved patient recognition and data interoperability. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.10.25333394, doi:10.1101/2025.08.10.25333394. This article has 3 citations.

  6. (lucano2025theorphanetnomenclature pages 26-29): C. Lucano, D. Lagorce, A. Olry, H. Ali, V. Lanneau, M. De Carvalho, A. Dilsizoglu Senol, M. Fructuoso, E. Gaillard, M.-C. Gaillard, S. Mihic, M. Tannoury, F. Sauvage, C. Rodwell, S. Maiella, M. Hanauer, and A. Rath. The orphanet nomenclature of rare diseases: a standard terminology for improved patient recognition and data interoperability. MedRxiv, Aug 2025. URL: https://doi.org/10.1101/2025.08.10.25333394, doi:10.1101/2025.08.10.25333394. This article has 3 citations.

  7. (vasilevsky2022mondounifyingdiseases pages 11-12): Nicole A Vasilevsky, Nicolas A Matentzoglu, Sabrina Toro, Joseph E Flack, Harshad Hegde, Deepak R Unni, Gioconda F Alyea, Joanna S Amberger, Larry Babb, James P Balhoff, Taylor I Bingaman, Gully A Burns, Orion J Buske, Tiffany J Callahan, Leigh C Carmody, Paula Carrio Cordo, Lauren E Chan, George S Chang, Sean L Christiaens, Michel Dumontier, Laura E Failla, May J Flowers, H. Alpha Garrett, Jennifer L Goldstein, Dylan Gration, Tudor Groza, Marc Hanauer, Nomi L Harris, Jason A Hilton, Daniel S Himmelstein, Charles Tapley Hoyt, Megan S Kane, Sebastian Köhler, David Lagorce, Abbe Lai, Martin Larralde, Antonia Lock, Irene López Santiago, Donna R Maglott, Adriana J Malheiro, Birgit H M Meldal, Monica C Munoz-Torres, Tristan H Nelson, Frank W Nicholas, David Ochoa, Daniel P Olson, Tudor I Oprea, David Osumi-Sutherland, Helen Parkinson, Zoë May Pendlington, Ana Rath, Heidi L Rehm, Lyubov Remennik, Erin R Riggs, Paola Roncaglia, Justyne E Ross, Marion F Shadbolt, Kent A Shefchek, Morgan N Similuk, Nicholas Sioutos, Damian Smedley, Rachel Sparks, Ray Stefancsik, Ralf Stephan, Andrea L Storm, Doron Stupp, Gregory S Stupp, Jagadish Chandrabose Sundaramurthi, Imke Tammen, Darin Tay, Courtney L Thaxton, Eloise Valasek, Jordi Valls-Margarit, Alex H Wagner, Danielle Welter, Patricia L Whetzel, Lori L Whiteman, Valerie Wood, Colleen H Xu, Andreas Zankl, Xingmin Aaron Zhang, Christopher G Chute, Peter N Robinson, Christopher J Mungall, Ada Hamosh, and Melissa A Haendel. Mondo: unifying diseases for the world, by the world. MedRxiv, Apr 2022. URL: https://doi.org/10.1101/2022.04.13.22273750, doi:10.1101/2022.04.13.22273750. This article has 158 citations.

  8. (vasilevsky2022mondounifyingdiseases pages 6-11): Nicole A Vasilevsky, Nicolas A Matentzoglu, Sabrina Toro, Joseph E Flack, Harshad Hegde, Deepak R Unni, Gioconda F Alyea, Joanna S Amberger, Larry Babb, James P Balhoff, Taylor I Bingaman, Gully A Burns, Orion J Buske, Tiffany J Callahan, Leigh C Carmody, Paula Carrio Cordo, Lauren E Chan, George S Chang, Sean L Christiaens, Michel Dumontier, Laura E Failla, May J Flowers, H. Alpha Garrett, Jennifer L Goldstein, Dylan Gration, Tudor Groza, Marc Hanauer, Nomi L Harris, Jason A Hilton, Daniel S Himmelstein, Charles Tapley Hoyt, Megan S Kane, Sebastian Köhler, David Lagorce, Abbe Lai, Martin Larralde, Antonia Lock, Irene López Santiago, Donna R Maglott, Adriana J Malheiro, Birgit H M Meldal, Monica C Munoz-Torres, Tristan H Nelson, Frank W Nicholas, David Ochoa, Daniel P Olson, Tudor I Oprea, David Osumi-Sutherland, Helen Parkinson, Zoë May Pendlington, Ana Rath, Heidi L Rehm, Lyubov Remennik, Erin R Riggs, Paola Roncaglia, Justyne E Ross, Marion F Shadbolt, Kent A Shefchek, Morgan N Similuk, Nicholas Sioutos, Damian Smedley, Rachel Sparks, Ray Stefancsik, Ralf Stephan, Andrea L Storm, Doron Stupp, Gregory S Stupp, Jagadish Chandrabose Sundaramurthi, Imke Tammen, Darin Tay, Courtney L Thaxton, Eloise Valasek, Jordi Valls-Margarit, Alex H Wagner, Danielle Welter, Patricia L Whetzel, Lori L Whiteman, Valerie Wood, Colleen H Xu, Andreas Zankl, Xingmin Aaron Zhang, Christopher G Chute, Peter N Robinson, Christopher J Mungall, Ada Hamosh, and Melissa A Haendel. Mondo: unifying diseases for the world, by the world. MedRxiv, Apr 2022. URL: https://doi.org/10.1101/2022.04.13.22273750, doi:10.1101/2022.04.13.22273750. This article has 158 citations.

  9. (sholeh2024epidemiologyoftularemia pages 1-2): Mohammad Sholeh, Safoura Moradkasani, and Saber Esmaeili. Epidemiology of tularemia in the countries of the who eastern mediterranean region (emro): a systematic review and meta-analysis. PLOS Neglected Tropical Diseases, 18:e0012141, May 2024. URL: https://doi.org/10.1371/journal.pntd.0012141, doi:10.1371/journal.pntd.0012141. This article has 11 citations and is from a domain leading peer-reviewed journal.

  10. (maurin2024nonvaccinalprophylaxisof pages 1-2): Max Maurin, Aurélie Hennebique, Camille Brunet, Léa Pondérand, Isabelle Pelloux, Sandrine Boisset, and Yvan Caspar. Non-vaccinal prophylaxis of tularemia. Frontiers in Microbiology, Nov 2024. URL: https://doi.org/10.3389/fmicb.2024.1507469, doi:10.3389/fmicb.2024.1507469. This article has 2 citations and is from a peer-reviewed journal.

  11. (sharma2023tularemia–a pages 2-3): Rinku Sharma, Rajendra Damu Patil, Birbal Singh, Sandip Chakraborty, Deepak Chandran, Kuldeep Dhama, Devi Gopinath, Gauri Jairath, Ajayta Rialch, Gorakh Mal, Putan Singh, Wanpen Chaicumpa, and G. Saikumar. Tularemia – a re-emerging disease with growing concern. Veterinary Quarterly, 43:1-16, Nov 2023. URL: https://doi.org/10.1080/01652176.2023.2277753, doi:10.1080/01652176.2023.2277753. This article has 48 citations and is from a domain leading peer-reviewed journal.

Artifacts