Anthrax

Infectious Disease MONDO:0005119 Pathograph 25 Show in embeddings browser Bacterial Infection Zoonotic Disease

Anthrax is a zoonotic bacterial infection caused by the spore-forming Gram-positive bacillus Bacillus anthracis. Humans acquire disease from environmentally persistent spores through cutaneous inoculation, inhalation, ingestion, or injection of contaminated material. After macrophage uptake and pXO1-dependent intracellular escape, vegetative bacilli evade phagocytosis with the pXO2 capsule and secrete protective-antigen-delivered lethal and edema toxins that disable MAPK signaling, raise intracellular cAMP, injure vascular endothelium, and can drive edema, bacteremia, sepsis, hemorrhagic meningitis, and shock.

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8
Pathophys.
13
Phenotypes
25
Pathograph
4
Medical Actions
5
Subtypes
2
References
1
Deep Research
🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES
◆

Subtypes

5
Cutaneous anthrax MONDO:0004215
The common skin form caused by direct inoculation of spores through skin, classically forming a pruritic papule, vesicles, edema, and a necrotic eschar.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Cutaneous anthrax, which results from direct inoculation of spores through the skin, is the most common form and accounts for >95% of human cases."
CDC guidelines define cutaneous anthrax by direct spore inoculation through skin and identify it as the dominant human presentation.
Inhalational anthrax MONDO:0016595
The aerosol-spore form that begins nonspecifically and can progress to hemorrhagic mediastinitis, dyspnea, pleural effusions, respiratory failure, shock, and meningitis.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Inhalation anthrax results from the inhalation of aerosolized spores."
CDC guidelines define inhalational anthrax by aerosol-spore inhalation.
Gastrointestinal anthrax MONDO:0001701
Ingestion anthrax acquired from contaminated meat, with intestinal lesions that can progress to abdominal pain, vomiting, bloody diarrhea, ascites, toxemia, and shock.
Show evidence (1 reference)
PMID:36980364 SUPPORT Other
"The infection occurs within 3-7 days following the ingestion of B. anthracis within contaminated food or drinks."
This review defines the ingestion route that produces gastrointestinal anthrax.
Oropharyngeal anthrax MONDO:0000236
The upper-aerodigestive form of ingestion anthrax, presenting with fever, sore throat, dysphagia, hoarseness, regional lymphadenopathy, and neck soft tissue edema.
Show evidence (1 reference)
PMID:36980364 SUPPORT Other
"Two clinical forms are described in the literature: oropharyngeal and gastrointestinal"
The review separates oropharyngeal anthrax from intestinal gastrointestinal disease after ingestion exposure.
Injection anthrax MONDO:0850618
A deep soft-tissue form caused by injecting spore-contaminated heroin or other contaminated injected material, often without the classic eschar and with risk of toxemia and sepsis.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Injection anthrax, which is a relatively new form, results from injection of heroin contaminated with B. anthracis spores."
CDC guidelines define injection anthrax by injection of spore-contaminated heroin.
⚙

Pathophysiology

8
Spore Uptake and Germination
Dormant endospores enter through skin, gut, lung, or injection-site tissue, are engulfed by regional macrophages, and germinate to vegetative bacilli during the first intracellular stage of infection.
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.
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
pXO1-Dependent Macrophage Escape Germinating spores become vegetative bacilli that escape macrophage phagocytic vesicles.
Show evidence (1 reference)
PMID:11207600 SUPPORT In Vitro
"Anthrax infections are initiated by dormant endospores gaining access to the mammalian host and becoming engulfed by regional macrophages (Mphi)."
The experimental study places endospore uptake by regional macrophages at the start of B. anthracis infection.
pXO1-Dependent Macrophage Escape
Newly vegetative bacilli escape from macrophage phagocytic vesicles into the cytoplasm, and that macrophage-release phenotype requires the pXO1 transactivator atxA even when the toxin genes themselves are absent.
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.
Downstream
Capsule-Mediated Immune Evasion Escaped vegetative bacilli activate capsule synthesis and resist phagocytic clearance.
Show evidence (1 reference)
PMID:11207600 SUPPORT In Vitro
"Genetic analysis from this study indicates that the toxin plasmid pXO1 is required for release from the Mphi, whereas the capsule plasmid pXO2 is not."
Establishes the pXO1 dependence of the early macrophage-escape step.
Capsule-Mediated Immune Evasion
Vegetative bacilli that carry the pXO2 plasmid synthesize the polyglutamate capsule, preventing efficient phagocytosis and enabling extracellular proliferation and bacteremia.
defense response to Gram-positive bacterium GO:0050830 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased defense response to Gram-positive bacterium (GO:0050830). GO:0050830 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Protective Antigen-Mediated Toxin Entry Extracellular bacilli secrete protective antigen with lethal factor and edema factor.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"The capsule prevents phagocytosis of the vegetative form of B. anthracis by macrophages, allowing it to evade the immune system."
CDC guidelines describe the antiphagocytic capsule as an immune-evasion virulence factor.
Protective Antigen-Mediated Toxin Entry
Protective antigen binds host anthrax toxin receptors such as ANTXR2/CMG2 and mediates entry of lethal factor and edema factor into toxin-sensitive host cells by endocytic uptake.
receptor-mediated endocytosis GO:0006898 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased receptor-mediated endocytosis (GO:0006898). GO:0006898 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Lethal Toxin MAPKK Cleavage Once PA delivers lethal factor into the cytosol, lethal factor perturbs host MAPK signaling.
Edema Toxin Activity PA also delivers edema factor into host cells, where edema toxin activity begins.
Show evidence (1 reference)
PMID:42409807 SUPPORT Model Organism
"CMG2/ANTXR2 functions as a Collagen VI receptor required for extracellular matrix homeostasis and as the primary portal for anthrax toxin entry."
Identifies ANTXR2/CMG2 as the primary receptor portal that allows anthrax toxin uptake in vivo.
Lethal Toxin MAPKK Cleavage
Once protective antigen delivers lethal factor into the cytosol, lethal factor cleaves the N-terminus of MAP kinase kinases (MEK1/2/3), disabling MAPK signaling and suppressing innate and adaptive immune responses.
MAPK cascade GO:0000165 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased MAPK cascade (GO:0000165). GO:0000165 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Lethal Toxin-Mediated Endothelial Apoptosis Lethal-toxin activity in the vasculature drives endothelial cell apoptosis.
Systemic Toxemia Toxin-driven immune suppression permits unchecked bacterial proliferation and systemic toxemia.
Show evidence (2 references)
PMID:42409807 SUPPORT Model Organism
"In the cytosol, LF eventually cleaves the N-terminus of MAP kinase kinases such as MEK1, 2 or 3"
Identifies lethal factor's cleavage of MAP kinase kinases as the molecular lesion that disables MAPK signaling.
PMID:37963097 SUPPORT REVIEW SYNTHESIS Other
"The two toxins also facilitate immune system evasion by disrupting various immune cell functions (e.g., cellular signaling and cell migration)"
CDC guidelines describe toxin-driven disruption of immune cell signaling as the basis of anthrax immune evasion.
Edema Toxin Activity
Protective antigen also delivers edema factor into host cells; edema toxin is one of the two secreted exotoxins responsible for the characteristic symptoms of anthrax, and its activity contributes to the tissue edema of anthrax lesions.
Downstream
Edema Edema toxin activity and vascular injury produce prominent tissue edema.
Show evidence (2 references)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Other
"The tripartite toxin comprises protective antigen (PA), lethal factor (LF) and edema factor (EF)"
Names edema factor as a distinct component of the tripartite anthrax toxin, delivered by protective antigen.
PMID:36980364 SUPPORT REVIEW SYNTHESIS Other
"The toxins are secreted the during multiplication of the vegetative B. anthracis and are responsible for the characteristic symptoms of anthrax"
Attributes the characteristic symptoms of anthrax, including tissue edema, to the secreted toxins.
Lethal Toxin-Mediated Endothelial Apoptosis
Lethal toxin causes apoptosis of vascular endothelial cells, contributing to hemorrhage and the capillary leak of systemic anthrax.
endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology.
Downstream
Shock Endothelial injury and capillary leak drive hypotension and shock in systemic anthrax.
Show evidence (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Other
"Lethal toxin causes apoptosis of endothelial cells within the vascular system and is thought to contribute to hemorrhage"
CDC guidelines attribute vascular endothelial apoptosis and hemorrhage to lethal toxin.
Systemic Toxemia
Toxin-driven immune suppression and continued vegetative growth allow unchecked proliferation and systemic toxemia.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Eschar Local toxin activity and tissue injury at a skin inoculation site produce the eschar of cutaneous anthrax.
Fever Systemic toxemia produces fever across the portal-of-entry forms.
Lymphadenopathy Regional and systemic spread produces lymphadenopathy, associated with early fatal outcomes.
Dyspnea Mediastinal disease and pleural effusions in inhalational anthrax cause dyspnea.
Pleural Effusion Inhalational anthrax characteristically produces large, lethal-factor-rich pleural effusions.
Respiratory Failure Reaccumulating pleural effusions and systemic toxemia can progress to respiratory failure.
Ascites Ingestion anthrax commonly produces massive ascites, a further lethal-factor reservoir.
Sepsis Systemic vegetative growth and toxemia manifest as sepsis.
Meningitis Disseminated bacilli can invade the meninges and produce anthrax meningitis.
Abdominal Pain Intestinal mucosal infection and edema produce abdominal pain in gastrointestinal anthrax.
Vomiting Gastrointestinal anthrax produces nausea and vomiting during intestinal disease.
Show evidence (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Other
"These combined effects allow bacterial proliferation and lead to the high morbidity and mortality associated with anthrax."
CDC guidelines synthesize the capsule and toxin effects as the proximate drivers of severe anthrax morbidity and mortality.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Anthrax 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

13
Cardiovascular 2
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 (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Human Clinical
"Lymphadenopathy was associated with fatal outcomes within the first 3 days of hospitalization, and abdominal pain was associated with later fatal outcomes"
CDC guidelines associate lymphadenopathy with early anthrax fatality.
Shock HP:0031273 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Shock (HP:0031273). HP:0031273 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"massive ascites followed by toxemia and shock which results in death"
The review names shock as the terminal event of progressive systemic anthrax.
Digestive 2
Vomiting HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"The initial symptoms of intestinal anthrax include fever, nausea, vomiting, anorexia and diarrhea."
The review lists vomiting among the initial symptoms of intestinal anthrax.
Ascites HP:0001541 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ascites (HP:0001541). HP:0001541 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Human Clinical
"Ascites was observed in 52% of adults with ingestion anthrax"
CDC guidelines report ascites in 52% of adults with ingestion anthrax.
Immune 2
Sepsis HP:0100806 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sepsis (HP:0100806). HP:0100806 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38638828 SUPPORT BACKGROUND Human Clinical
"The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis"
This human case report's introduction summarizes sepsis as a complication of all major anthrax forms.
Meningitis HP:0001287 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Meningitis (HP:0001287). HP:0001287 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Human Clinical
"Anthrax meningitis can complicate any form of anthrax or occur alone."
CDC guidelines describe meningitis as a cross-form complication.
Integument 1
Eschar HP:6000793 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Eschar (HP:6000793). HP:6000793 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"The formation of the eschar its subsequent resolution can take 2-6 weeks, regardless of treatment"
The review describes eschar formation as part of the cutaneous anthrax lesion.
Metabolism 3
Edema HP:0000969 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Edema (HP:0000969). HP:0000969 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"A lesion begins as a pruritic papule and typically progresses to a ring of vesicles surrounded by erythema and edema within 2-4 days"
The review names edema as part of the characteristic cutaneous lesion evolution.
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:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"Following an incubation period of 1-7 days, nonspecific initial symptoms including mild fever, fatigue, malaise, myalgia, nonproductive cough and some chest or abdominal pain are seen"
The review lists fever among the early manifestations of inhalational anthrax.
Pleural Effusion HP:0002202 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pleural effusion (HP:0002202). HP:0002202 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Human Clinical
"pleural effusion was most commonly a complication of inhalation anthrax (76%)"
CDC guidelines report pleural effusion in 76% of inhalational anthrax cases.
Respiratory 2
Dyspnea HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"The disease progresses to the severe phase which is characterized by high fever, toxemia, dyspnea and cyanosis."
The review lists dyspnea among severe-phase manifestations of inhalational anthrax.
Respiratory Failure HP:0002878 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory failure (HP:0002878). HP:0002878 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"In inhalation anthrax, patients may require mechanical ventilation due to respiratory failure caused by reaccumulating pleural effusions."
The review describes respiratory failure in inhalational anthrax as a consequence of recurrent pleural effusions.
Constitutional 1
Abdominal Pain HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027). HP:0002027 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"As the infection progresses, symptoms include acute abdominal pain, hematemesis, bloody diarrhea and massive ascites followed by toxemia and shock which results in death."
The review lists acute abdominal pain among progressive intestinal anthrax manifestations.
💊

Medical Actions

4
Antimicrobial Therapy
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: ciprofloxacin NCIT:C375 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses ciprofloxacin (NCIT:C375). NCIT:C375 is a therapeutic agent from the NCI Thesaurus. doxycycline NCIT:C457 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses doxycycline (NCIT:C457). NCIT:C457 is a therapeutic agent from the NCI Thesaurus. levofloxacin NCIT:C1586 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses levofloxacin (NCIT:C1586). NCIT:C1586 is a therapeutic agent from the NCI Thesaurus. minocycline NCIT:C61849 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses minocycline (NCIT:C61849). NCIT:C61849 is a therapeutic agent from the NCI Thesaurus. penicillin G NCIT:C61883 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses penicillin G (NCIT:C61883). NCIT:C61883 is a therapeutic agent from the NCI Thesaurus. tetracycline NCIT:C865 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses tetracycline (NCIT:C865). NCIT:C865 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Anthrax treatment and postexposure prophylaxis use antibiotics with activity against B. anthracis; ciprofloxacin, doxycycline, levofloxacin, minocycline, penicillin G, and tetracycline are FDA-approved for anthrax PEP, treatment, or both, with broader alternatives in CDC guidance for contraindications, intolerance, limited supply, or engineered resistance.
Mechanism Target:
Capsule-Mediated Immune Evasion — Effective antibiotics kill vegetative B. anthracis and interrupt extracellular proliferation before toxin-driven systemic injury becomes irreversible.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Ciprofloxacin, doxycycline, levofloxacin, minocycline, penicillin G, and tetracycline are approved by FDA for anthrax PEPAbx, treatment, or both"
The 2023 CDC guideline enumerates FDA-approved antimicrobial options for anthrax postexposure prophylaxis and treatment.
Pleural Fluid Drainage
Action: pleural fluid drainageNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is pleural fluid drainage, annotated with Thoracentesis (NCIT:C15392). NCIT:C15392 is a clinical intervention from the NCI Thesaurus. Ontology label: Thoracentesis NCIT:C15392
Platform: Surgery
Drainage of the large, lethal-factor-rich pleural effusions of inhalational anthrax by thoracentesis or chest-tube placement relieves mechanical lung compression and removes a reservoir of anthrax lethal factor, and is associated with improved survival.
Mechanism Target:
Pleural Effusion — Draining the effusion directly relieves the mechanical lung compression it causes.
Systemic Toxemia — The drained fluid is a reservoir of lethal factor, so its removal lowers systemic toxin load.
Show evidence (2 references)
PMID:37963097 SUPPORT REVIEW SYNTHESIS Human Clinical
"drainage of pleural fluid is believed to improve survival by decreasing mechanical lung compression"
CDC guidelines present pleural fluid drainage as survival-improving in inhalational anthrax.
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"this procedure improved outcomes in a series of cases by decreasing the level of lethal factors and mechanical lung compression"
The review reports improved outcomes from pleural drainage, attributed to lowering lethal-factor levels and lung compression.
Anthrax Antitoxin
Action: Passive ImmunizationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Passive Immunization (NCIT:C15259). NCIT:C15259 is a clinical intervention from the NCI Thesaurus. NCIT:C15259
Platform: Other
Antitoxins such as anthrax immunoglobulin intravenous, obiltoxaximab, and raxibacumab neutralize circulating toxin and are considered adjunctive countermeasures for systemic anthrax.
Mechanism Target:
Protective Antigen-Mediated Toxin Entry — Anthrax antitoxins neutralize protective antigen-dependent toxin entry upstream of lethal factor and edema factor cytosolic delivery.
Show evidence (1 reference)
PMID:37963097 SUPPORT Model Organism
"In animal models, treatment with the polyclonal or either monoclonal antitoxin provided a statistically significant (p<=0.0001for all three antitoxins) survival benefit compared with no treatment."
CDC's systematic review found animal efficacy evidence for polyclonal AIGIV and the monoclonal antitoxins obiltoxaximab and raxibacumab.
Postexposure Anthrax Vaccination
Action: VaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. NCIT:C15346
Platform: Vaccine
Anthrax vaccination is paired with antimicrobial postexposure prophylaxis after exposure of an unvaccinated or incompletely vaccinated person so delayed spore germination can be covered after antimicrobial therapy stops.
Mechanism Target:
Protective Antigen-Mediated Toxin Entry — Human anthrax vaccines use protective antigen as the principal immunogen, priming antibody responses that neutralize protective antigen-dependent toxin entry if spores germinate after antibiotic prophylaxis ends.
Show evidence (1 reference)
PMID:36980364 SUPPORT Other
"Protective antigen is the principal protective immunogen in these licensed human vaccines"
Identifies protective antigen, the shared delivery component for lethal and edema toxins, as the immunogen targeted by licensed human vaccines.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"For unvaccinated or incompletely vaccinated persons exposed to B. anthracis, PEP includes both antimicrobial drugs with activity against B. anthracis (PEPAbx) and anthrax vaccine (PEPVx)."
CDC guidelines pair antibiotic prophylaxis with vaccination after exposure in people who are not fully vaccinated.
🔬

Diagnosis

1
Culture and molecular confirmation of B. anthracis
Anthrax is confirmed by bacterial culture and molecular testing. B. anthracis grows as non-hemolytic, non-motile colonies and is distinguished from other Bacillus species by gamma-phage susceptibility and penicillin susceptibility; multiplex PCR targeting the pXO1 (lef) and pXO2 (capB) virulence markers gives specific molecular identification.
bacterial culture and molecular detection NCIT:C17003 NCI Thesaurus (NCIT)
Show evidence (3 references)
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"The symptoms of anthrax in the early stage mimics many diseases and as a consequence it is important to confirm the diagnosis using a bacterial culture or a molecular test"
The review states that culture or molecular testing is required to confirm anthrax.
PMID:36980364 SUPPORT REVIEW SYNTHESIS Human Clinical
"anthracis can be differentiated from other Bacillus species using a range of simple first-line laboratory tests which include gamma phage susceptibility, catalase production, lack of motility, lack of hemolytic activity when cultured on blood agar and susceptibility to penicillin"
The review lists the first-line phenotypic tests that differentiate B. anthracis.
PMID:33371332 SUPPORT In Vitro
"Specifically, the assay targeted the lef (pXO1) and capB (pXO2) virulence markers of B"
This assay development study targets the pXO1 lef and pXO2 capB markers for molecular detection of B. anthracis.
🦠

Infectious Agent

1
Bacillus anthracis
Gram-positive, aerobic, spore-forming, nonmotile bacillus whose virulence depends on the pXO1 toxin plasmid and the pXO2 polyglutamate capsule plasmid.
Bacillus anthracis NCBITaxon:1392 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:36980364 SUPPORT Other
"The etiological agent is Bacillus anthracis which is a Gram-positive, aerobic, spore-forming, nonmotile, rod-shaped bacillus."
Identifies B. anthracis and describes the bacterial morphology underlying the agent record.
↔️

Transmission

4
Contact with infected animals or animal products
Direct handling of ill or dead animals and contaminated hides, wool, hair, leather, or bone meal exposes skin abrasions to spores and initiates most natural cutaneous infections.
Show evidence (1 reference)
PMID:26720232 SUPPORT Human Clinical
"All patients had histories of contact with diseased animals and animal products."
This 82-patient endemic-region series links human cutaneous anthrax to contact with diseased animals or their products.
Inhalation of aerosolized spores
Aerosolized spores from contaminated animal products, industrial exposure, or intentional release can be inhaled and produce inhalational anthrax.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Inhalation anthrax results from the inhalation of aerosolized spores."
CDC guidelines state that aerosolized spores are the route for inhalational anthrax.
Ingestion of contaminated meat
Eating meat from infected animals delivers spores to the gastrointestinal tract and can cause intestinal or oropharyngeal anthrax.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Ingestion anthrax usually results from consumption of infected meat."
CDC guidelines identify contaminated meat ingestion as the usual route for ingestion anthrax.
Injection of contaminated heroin
Injection of heroin contaminated with B. anthracis spores introduces the pathogen into deep soft tissue.
Show evidence (1 reference)
PMID:37963097 SUPPORT Other
"Injection anthrax, which is a relatively new form, results from injection of heroin contaminated with B. anthracis spores."
CDC guidelines identify contaminated heroin injection as the route for injection anthrax.
{ }

Source YAML

click to show 
name: Anthrax
creation_date: "2026-09-25T02:51:11Z"
category: Infectious Disease
description: >-
  Anthrax is a zoonotic bacterial infection caused by the spore-forming
  Gram-positive bacillus Bacillus anthracis. Humans acquire disease from
  environmentally persistent spores through cutaneous inoculation, inhalation,
  ingestion, or injection of contaminated material. After macrophage uptake and
  pXO1-dependent intracellular escape, vegetative bacilli evade phagocytosis
  with the pXO2 capsule and secrete protective-antigen-delivered lethal and
  edema toxins that disable MAPK signaling, raise intracellular cAMP, injure
  vascular endothelium, and can drive edema, bacteremia, sepsis, hemorrhagic
  meningitis, and shock.
disease_term:
  preferred_term: anthrax infection
  term:
    id: MONDO:0005119
    label: anthrax infection
parents:
- Bacterial Infection
- Zoonotic Disease
synonyms:
- Bacillus anthracis infection
- malignant pustule
- woolsorters' disease
- splenic fever
references:
- reference: PMID:36980364
  title: "Human Anthrax: Update of the Diagnosis and Treatment."
- reference: PMID:37963097
  title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:33371332
      reference_title: TaqMan Assays for Simultaneous Detection of Bacillus anthracis and Bacillus cereus biovar anthracis.
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: BACKGROUND
      snippet: >-
        Anthrax is a worldwide zoonotic disease caused by the spore-forming bacterium
        Bacillus anthracis.
      explanation: >-
        Anthrax is a bacterial zoonosis, placing it in Harrison's Infectious
        Diseases Part.
has_subtypes:
- name: Cutaneous
  display_name: Cutaneous anthrax
  description: >-
    The common skin form caused by direct inoculation of spores through skin,
    classically forming a pruritic papule, vesicles, edema, and a necrotic
    eschar.
  subtype_term:
    preferred_term: cutaneous anthrax
    term:
      id: MONDO:0004215
      label: cutaneous anthrax
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Cutaneous anthrax, which results from direct inoculation of spores through
      the skin, is the most common form and accounts for >95% of human cases.
    explanation: >-
      CDC guidelines define cutaneous anthrax by direct spore inoculation through
      skin and identify it as the dominant human presentation.
- name: Inhalational
  display_name: Inhalational anthrax
  description: >-
    The aerosol-spore form that begins nonspecifically and can progress to
    hemorrhagic mediastinitis, dyspnea, pleural effusions, respiratory failure,
    shock, and meningitis.
  subtype_term:
    preferred_term: inhalational anthrax
    term:
      id: MONDO:0016595
      label: inhalational anthrax
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Inhalation anthrax results from the inhalation of aerosolized spores.
    explanation: >-
      CDC guidelines define inhalational anthrax by aerosol-spore inhalation.
- name: Gastrointestinal
  display_name: Gastrointestinal anthrax
  description: >-
    Ingestion anthrax acquired from contaminated meat, with intestinal lesions
    that can progress to abdominal pain, vomiting, bloody diarrhea, ascites,
    toxemia, and shock.
  subtype_term:
    preferred_term: gastrointestinal anthrax
    term:
      id: MONDO:0001701
      label: gastrointestinal anthrax
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The infection occurs within 3-7 days following the ingestion of B. anthracis
      within contaminated food or drinks.
    explanation: >-
      This review defines the ingestion route that produces gastrointestinal
      anthrax.
- name: Oropharyngeal
  display_name: Oropharyngeal anthrax
  description: >-
    The upper-aerodigestive form of ingestion anthrax, presenting with fever,
    sore throat, dysphagia, hoarseness, regional lymphadenopathy, and neck soft
    tissue edema.
  subtype_term:
    preferred_term: oropharyngeal anthrax
    term:
      id: MONDO:0000236
      label: oropharyngeal anthrax
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Two clinical forms are described in the literature: oropharyngeal and
      gastrointestinal
    explanation: >-
      The review separates oropharyngeal anthrax from intestinal gastrointestinal
      disease after ingestion exposure.
- name: Injection
  display_name: Injection anthrax
  description: >-
    A deep soft-tissue form caused by injecting spore-contaminated heroin or
    other contaminated injected material, often without the classic eschar and
    with risk of toxemia and sepsis.
  subtype_term:
    preferred_term: injection anthrax
    term:
      id: MONDO:0850618
      label: injection anthrax
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Injection anthrax, which is a relatively new form, results from injection of
      heroin contaminated with B. anthracis spores.
    explanation: >-
      CDC guidelines define injection anthrax by injection of spore-contaminated
      heroin.
infectious_agent:
- name: Bacillus anthracis
  description: >-
    Gram-positive, aerobic, spore-forming, nonmotile bacillus whose virulence
    depends on the pXO1 toxin plasmid and the pXO2 polyglutamate capsule
    plasmid.
  infectious_agent_term:
    preferred_term: Bacillus anthracis
    term:
      id: NCBITaxon:1392
      label: Bacillus anthracis
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The etiological agent is Bacillus anthracis which is a Gram-positive,
      aerobic, spore-forming, nonmotile, rod-shaped bacillus.
    explanation: >-
      Identifies B. anthracis and describes the bacterial morphology underlying
      the agent record.
transmission:
- name: Contact with infected animals or animal products
  description: >-
    Direct handling of ill or dead animals and contaminated hides, wool, hair,
    leather, or bone meal exposes skin abrasions to spores and initiates most
    natural cutaneous infections.
  evidence:
  - reference: PMID:26720232
    reference_title: "Human Cutaneous Anthrax, the East Anatolian Region of Turkey 2008-2014."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients had histories of contact with diseased animals and animal
      products.
    explanation: >-
      This 82-patient endemic-region series links human cutaneous anthrax to
      contact with diseased animals or their products.
- name: Inhalation of aerosolized spores
  description: >-
    Aerosolized spores from contaminated animal products, industrial exposure, or
    intentional release can be inhaled and produce inhalational anthrax.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Inhalation anthrax results from the inhalation of aerosolized spores.
    explanation: >-
      CDC guidelines state that aerosolized spores are the route for inhalational
      anthrax.
- name: Ingestion of contaminated meat
  description: >-
    Eating meat from infected animals delivers spores to the gastrointestinal
    tract and can cause intestinal or oropharyngeal anthrax.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Ingestion anthrax usually results from consumption of infected meat.
    explanation: >-
      CDC guidelines identify contaminated meat ingestion as the usual route for
      ingestion anthrax.
- name: Injection of contaminated heroin
  description: >-
    Injection of heroin contaminated with B. anthracis spores introduces the
    pathogen into deep soft tissue.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Injection anthrax, which is a relatively new form, results from injection of
      heroin contaminated with B. anthracis spores.
    explanation: >-
      CDC guidelines identify contaminated heroin injection as the route for
      injection anthrax.
pathophysiology:
- name: Spore Uptake and Germination
  description: >-
    Dormant endospores enter through skin, gut, lung, or injection-site tissue,
    are engulfed by regional macrophages, and germinate to vegetative bacilli
    during the first intracellular stage of infection.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: phagocytosis
    term:
      id: GO:0006909
      label: phagocytosis
  evidence:
  - reference: PMID:11207600
    reference_title: "Early Bacillus anthracis-macrophage interactions: intracellular survival survival and escape."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Anthrax infections are initiated by dormant endospores gaining access to the
      mammalian host and becoming engulfed by regional macrophages (Mphi).
    explanation: >-
      The experimental study places endospore uptake by regional macrophages at
      the start of B. anthracis infection.
  downstream:
  - target: pXO1-Dependent Macrophage Escape
    causal_link_type: DIRECT
    description: >-
      Germinating spores become vegetative bacilli that escape macrophage
      phagocytic vesicles.
- name: pXO1-Dependent Macrophage Escape
  description: >-
    Newly vegetative bacilli escape from macrophage phagocytic vesicles into the
    cytoplasm, and that macrophage-release phenotype requires the pXO1
    transactivator atxA even when the toxin genes themselves are absent.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  evidence:
  - reference: PMID:11207600
    reference_title: "Early Bacillus anthracis-macrophage interactions: intracellular survival survival and escape."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Genetic analysis from this study indicates that the toxin plasmid pXO1 is
      required for release from the Mphi, whereas the capsule plasmid pXO2 is not.
    explanation: >-
      Establishes the pXO1 dependence of the early macrophage-escape step.
  downstream:
  - target: Capsule-Mediated Immune Evasion
    causal_link_type: DIRECT
    description: >-
      Escaped vegetative bacilli activate capsule synthesis and resist
      phagocytic clearance.
- name: Capsule-Mediated Immune Evasion
  description: >-
    Vegetative bacilli that carry the pXO2 plasmid synthesize the
    polyglutamate capsule, preventing efficient phagocytosis and enabling
    extracellular proliferation and bacteremia.
  biological_scale: CELLULAR
  biological_processes:
  - preferred_term: defense response to Gram-positive bacterium
    modifier: DECREASED
    term:
      id: GO:0050830
      label: defense response to Gram-positive bacterium
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The capsule prevents phagocytosis of the vegetative form of B. anthracis by
      macrophages, allowing it to evade the immune system.
    explanation: >-
      CDC guidelines describe the antiphagocytic capsule as an immune-evasion
      virulence factor.
  downstream:
  - target: Protective Antigen-Mediated Toxin Entry
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Extracellular bacilli secrete protective antigen with lethal factor and
      edema factor.
- name: Protective Antigen-Mediated Toxin Entry
  description: >-
    Protective antigen binds host anthrax toxin receptors such as ANTXR2/CMG2
    and mediates entry of lethal factor and edema factor into toxin-sensitive
    host cells by endocytic uptake.
  biological_scale: CELLULAR
  biological_processes:
  - preferred_term: receptor-mediated endocytosis
    modifier: INCREASED
    term:
      id: GO:0006898
      label: receptor-mediated endocytosis
  evidence:
  - reference: PMID:42409807
    reference_title: Dynamic S-acylation controls CMG2 maturation extracellular matrix regulation and anthrax toxin susceptibility in vivo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      CMG2/ANTXR2 functions as a Collagen VI receptor required for extracellular
      matrix homeostasis and as the primary portal for anthrax toxin entry.
    explanation: >-
      Identifies ANTXR2/CMG2 as the primary receptor portal that allows anthrax
      toxin uptake in vivo.
  downstream:
  - target: Lethal Toxin MAPKK Cleavage
    causal_link_type: DIRECT
    description: >-
      Once PA delivers lethal factor into the cytosol, lethal factor perturbs
      host MAPK signaling.
  - target: Edema Toxin Activity
    causal_link_type: DIRECT
    description: >-
      PA also delivers edema factor into host cells, where edema toxin activity
      begins.
- name: Lethal Toxin MAPKK Cleavage
  description: >-
    Once protective antigen delivers lethal factor into the cytosol, lethal
    factor cleaves the N-terminus of MAP kinase kinases (MEK1/2/3), disabling
    MAPK signaling and suppressing innate and adaptive immune responses.
  biological_scale: MOLECULAR
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: DECREASED
    term:
      id: GO:0000165
      label: MAPK cascade
  evidence:
  - reference: PMID:42409807
    reference_title: Dynamic S-acylation controls CMG2 maturation extracellular matrix regulation and anthrax toxin susceptibility in vivo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      In the cytosol, LF eventually cleaves the N-terminus of MAP kinase kinases
      such as MEK1, 2 or 3
    explanation: >-
      Identifies lethal factor's cleavage of MAP kinase kinases as the molecular
      lesion that disables MAPK signaling.
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The two toxins also facilitate immune system evasion by disrupting various
      immune cell functions (e.g., cellular signaling and cell migration)
    explanation: >-
      CDC guidelines describe toxin-driven disruption of immune cell signaling as
      the basis of anthrax immune evasion.
  downstream:
  - target: Lethal Toxin-Mediated Endothelial Apoptosis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Lethal-toxin activity in the vasculature drives endothelial cell apoptosis.
  - target: Systemic Toxemia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Toxin-driven immune suppression permits unchecked bacterial proliferation
      and systemic toxemia.
- name: Edema Toxin Activity
  description: >-
    Protective antigen also delivers edema factor into host cells; edema toxin
    is one of the two secreted exotoxins responsible for the characteristic
    symptoms of anthrax, and its activity contributes to the tissue edema of
    anthrax lesions.
  biological_scale: MOLECULAR
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The tripartite toxin comprises protective antigen (PA), lethal factor (LF)
      and edema factor (EF)
    explanation: >-
      Names edema factor as a distinct component of the tripartite anthrax toxin,
      delivered by protective antigen.
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The toxins are secreted the during multiplication of the vegetative
      B. anthracis and are responsible for the characteristic symptoms of anthrax
    explanation: >-
      Attributes the characteristic symptoms of anthrax, including tissue edema,
      to the secreted toxins.
  downstream:
  - target: Edema
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Edema toxin activity and vascular injury produce prominent tissue edema.
- name: Lethal Toxin-Mediated Endothelial Apoptosis
  description: >-
    Lethal toxin causes apoptosis of vascular endothelial cells, contributing to
    hemorrhage and the capillary leak of systemic anthrax.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Lethal toxin causes apoptosis of endothelial cells within the vascular
      system and is thought to contribute to hemorrhage
    explanation: >-
      CDC guidelines attribute vascular endothelial apoptosis and hemorrhage to
      lethal toxin.
  downstream:
  - target: Shock
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Endothelial injury and capillary leak drive hypotension and shock in
      systemic anthrax.
- name: Systemic Toxemia
  description: >-
    Toxin-driven immune suppression and continued vegetative growth allow
    unchecked proliferation and systemic toxemia.
  biological_scale: ORGANISM
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      These combined effects allow bacterial proliferation and lead to the high
      morbidity and mortality associated with anthrax.
    explanation: >-
      CDC guidelines synthesize the capsule and toxin effects as the proximate
      drivers of severe anthrax morbidity and mortality.
  downstream:
  - target: Eschar
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Local toxin activity and tissue injury at a skin inoculation site produce the eschar of cutaneous anthrax.
  - target: Fever
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic toxemia produces fever across the portal-of-entry forms.
  - target: Lymphadenopathy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Regional and systemic spread produces lymphadenopathy, associated with early fatal outcomes.
  - target: Dyspnea
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Mediastinal disease and pleural effusions in inhalational anthrax cause dyspnea.
  - target: Pleural Effusion
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Inhalational anthrax characteristically produces large, lethal-factor-rich pleural effusions.
  - target: Respiratory Failure
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Reaccumulating pleural effusions and systemic toxemia can progress to respiratory failure.
  - target: Ascites
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Ingestion anthrax commonly produces massive ascites, a further lethal-factor reservoir.
  - target: Sepsis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic vegetative growth and toxemia manifest as sepsis.
  - target: Meningitis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Disseminated bacilli can invade the meninges and produce anthrax meningitis.
  - target: Abdominal Pain
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Intestinal mucosal infection and edema produce abdominal pain in gastrointestinal anthrax.
  - target: Vomiting
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Gastrointestinal anthrax produces nausea and vomiting during intestinal disease.
phenotypes:
- name: Eschar
  subtype: Cutaneous
  description: >-
    Cutaneous anthrax lesions progress from a pruritic papule to vesicles and a
    black eschar over days.
  phenotype_term:
    preferred_term: Eschar
    term:
      id: HP:6000793
      label: Eschar
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The formation of the eschar its subsequent resolution can take 2-6 weeks,
      regardless of treatment
    explanation: >-
      The review describes eschar formation as part of the cutaneous anthrax
      lesion.
- name: Edema
  subtype: Cutaneous
  description: >-
    Vesicles at the skin inoculation site are surrounded by edema, and face or
    neck lesions can have extensive edema.
  phenotype_term:
    preferred_term: Edema
    term:
      id: HP:0000969
      label: Edema
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      A lesion begins as a pruritic papule and typically progresses to a ring of
      vesicles surrounded by erythema and edema within 2-4 days
    explanation: >-
      The review names edema as part of the characteristic cutaneous lesion
      evolution.
- name: Dyspnea
  subtype: Inhalational
  description: >-
    Inhalational anthrax can progress from nonspecific symptoms to a severe
    toxemic phase with dyspnea.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The disease progresses to the severe phase which is characterized by high
      fever, toxemia, dyspnea and cyanosis.
    explanation: >-
      The review lists dyspnea among severe-phase manifestations of inhalational
      anthrax.
- name: Respiratory Failure
  subtype: Inhalational
  description: >-
    Reaccumulating pleural effusions in inhalational anthrax can cause
    respiratory failure severe enough to require mechanical ventilation.
  phenotype_term:
    preferred_term: Respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In inhalation anthrax, patients may require mechanical ventilation due to
      respiratory failure caused by reaccumulating pleural effusions.
    explanation: >-
      The review describes respiratory failure in inhalational anthrax as a
      consequence of recurrent pleural effusions.
- name: Sepsis
  description: >-
    Each portal-of-entry form can disseminate and progress to anthrax sepsis.
  phenotype_term:
    preferred_term: Sepsis
    term:
      id: HP:0100806
      label: Sepsis
  evidence:
  - reference: PMID:38638828
    reference_title: "Case report: Cutaneous anthrax diagnosed using mNGS of a formalin-fixed paraffin-embedded tissue sample."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      The disease has four typical clinical forms, cutaneous, gastrointestinal,
      inhalation, and injection, all of which may result in sepsis or meningitis
    explanation: >-
      This human case report's introduction summarizes sepsis as a complication
      of all major anthrax forms.
- name: Meningitis
  description: >-
    B. anthracis dissemination can produce anthrax meningitis as a complication
    of any portal-of-entry form.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Anthrax meningitis can complicate any form of anthrax or occur alone.
    explanation: >-
      CDC guidelines describe meningitis as a cross-form complication.
- name: Abdominal Pain
  subtype: Gastrointestinal
  description: >-
    Intestinal anthrax can progress to acute abdominal pain as lesions develop
    along the gastrointestinal tract.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      As the infection progresses, symptoms include acute abdominal pain,
      hematemesis, bloody diarrhea and massive ascites followed by toxemia and
      shock which results in death.
    explanation: >-
      The review lists acute abdominal pain among progressive intestinal anthrax
      manifestations.
- name: Vomiting
  subtype: Gastrointestinal
  description: Fever, nausea, vomiting, anorexia, and diarrhea are early intestinal anthrax symptoms.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The initial symptoms of intestinal anthrax include fever, nausea, vomiting,
      anorexia and diarrhea.
    explanation: >-
      The review lists vomiting among the initial symptoms of intestinal anthrax.
- name: Fever
  description: Fever is a nonspecific early manifestation across the portal-of-entry forms.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Following an incubation period of 1-7 days, nonspecific initial symptoms
      including mild fever, fatigue, malaise, myalgia, nonproductive cough and
      some chest or abdominal pain are seen
    explanation: >-
      The review lists fever among the early manifestations of inhalational
      anthrax.
- name: Pleural Effusion
  subtype: Inhalational
  description: >-
    Inhalational anthrax characteristically produces large pleural effusions
    rich in anthrax lethal factor.
  phenotype_term:
    preferred_term: Pleural effusion
    term:
      id: HP:0002202
      label: Pleural effusion
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      pleural effusion was most commonly a complication of inhalation anthrax (76%)
    explanation: >-
      CDC guidelines report pleural effusion in 76% of inhalational anthrax cases.
- name: Ascites
  subtype: Gastrointestinal
  description: >-
    Ingestion (gastrointestinal) anthrax commonly produces massive ascites,
    which serves as a further reservoir for lethal factor.
  phenotype_term:
    preferred_term: Ascites
    term:
      id: HP:0001541
      label: Ascites
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Ascites was observed in 52% of adults with ingestion anthrax
    explanation: >-
      CDC guidelines report ascites in 52% of adults with ingestion anthrax.
- name: Lymphadenopathy
  description: >-
    Regional and systemic lymphadenopathy occurs across anthrax forms and is
    associated with early fatal outcomes.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Lymphadenopathy was associated with fatal outcomes within the first 3 days
      of hospitalization, and abdominal pain was associated with later fatal
      outcomes
    explanation: >-
      CDC guidelines associate lymphadenopathy with early anthrax fatality.
- name: Shock
  description: >-
    Progressive systemic toxemia culminates in shock, the terminal event across
    severe anthrax forms.
  phenotype_term:
    preferred_term: Shock
    term:
      id: HP:0031273
      label: Shock
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      massive ascites followed by toxemia and shock which results in death
    explanation: >-
      The review names shock as the terminal event of progressive systemic
      anthrax.
diagnosis:
- name: Culture and molecular confirmation of B. anthracis
  description: >-
    Anthrax is confirmed by bacterial culture and molecular testing. B. anthracis
    grows as non-hemolytic, non-motile colonies and is distinguished from other
    Bacillus species by gamma-phage susceptibility and penicillin susceptibility;
    multiplex PCR targeting the pXO1 (lef) and pXO2 (capB) virulence markers gives
    specific molecular identification.
  diagnosis_term:
    preferred_term: bacterial culture and molecular detection
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  evidence:
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The symptoms of anthrax in the early stage mimics many diseases and as a
      consequence it is important to confirm the diagnosis using a bacterial
      culture or a molecular test
    explanation: >-
      The review states that culture or molecular testing is required to confirm
      anthrax.
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      anthracis can be differentiated from other Bacillus species using a range
      of simple first-line laboratory tests which include gamma phage
      susceptibility, catalase production, lack of motility, lack of hemolytic
      activity when cultured on blood agar and susceptibility to penicillin
    explanation: >-
      The review lists the first-line phenotypic tests that differentiate
      B. anthracis.
  - reference: PMID:33371332
    reference_title: TaqMan Assays for Simultaneous Detection of Bacillus anthracis and Bacillus cereus biovar anthracis.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Specifically, the assay targeted the lef (pXO1) and capB (pXO2) virulence
      markers of B
    explanation: >-
      This assay development study targets the pXO1 lef and pXO2 capB markers for
      molecular detection of B. anthracis.
treatments:
- name: Antimicrobial Therapy
  description: >-
    Anthrax treatment and postexposure prophylaxis use antibiotics with activity
    against B. anthracis; ciprofloxacin, doxycycline, levofloxacin, minocycline,
    penicillin G, and tetracycline are FDA-approved for anthrax PEP, treatment,
    or both, with broader alternatives in CDC guidance for contraindications,
    intolerance, limited supply, or engineered resistance.
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: ciprofloxacin
      term:
        id: NCIT:C375
        label: Ciprofloxacin
    - preferred_term: doxycycline
      term:
        id: NCIT:C457
        label: Doxycycline
    - preferred_term: levofloxacin
      term:
        id: NCIT:C1586
        label: Levofloxacin
    - preferred_term: minocycline
      term:
        id: NCIT:C61849
        label: Minocycline
    - preferred_term: penicillin G
      term:
        id: NCIT:C61883
        label: Penicillin G
    - preferred_term: tetracycline
      term:
        id: NCIT:C865
        label: Tetracycline
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Capsule-Mediated Immune Evasion
    description: >-
      Effective antibiotics kill vegetative B. anthracis and interrupt
      extracellular proliferation before toxin-driven systemic injury becomes
      irreversible.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Ciprofloxacin, doxycycline, levofloxacin, minocycline, penicillin G, and
      tetracycline are approved by FDA for anthrax PEPAbx, treatment, or both
    explanation: >-
      The 2023 CDC guideline enumerates FDA-approved antimicrobial options for
      anthrax postexposure prophylaxis and treatment.
- name: Pleural Fluid Drainage
  description: >-
    Drainage of the large, lethal-factor-rich pleural effusions of inhalational
    anthrax by thoracentesis or chest-tube placement relieves mechanical lung
    compression and removes a reservoir of anthrax lethal factor, and is
    associated with improved survival.
  treatment_term:
    preferred_term: pleural fluid drainage
    term:
      id: NCIT:C15392
      label: Thoracentesis
  therapeutic_modality: SURGERY
  target_mechanisms:
  - target: Pleural Effusion
    description: >-
      Draining the effusion directly relieves the mechanical lung compression it
      causes.
  - target: Systemic Toxemia
    description: >-
      The drained fluid is a reservoir of lethal factor, so its removal lowers
      systemic toxin load.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      drainage of pleural fluid is believed to improve survival by decreasing
      mechanical lung compression
    explanation: >-
      CDC guidelines present pleural fluid drainage as survival-improving in
      inhalational anthrax.
  - reference: PMID:36980364
    reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      this procedure improved outcomes in a series of cases by decreasing the
      level of lethal factors and mechanical lung compression
    explanation: >-
      The review reports improved outcomes from pleural drainage, attributed to
      lowering lethal-factor levels and lung compression.
- name: Anthrax Antitoxin
  description: >-
    Antitoxins such as anthrax immunoglobulin intravenous, obiltoxaximab, and
    raxibacumab neutralize circulating toxin and are considered adjunctive
    countermeasures for systemic anthrax.
  treatment_term:
    preferred_term: Passive Immunization
    term:
      id: NCIT:C15259
      label: Passive Immunization
  therapeutic_modality: OTHER
  target_mechanisms:
  - target: Protective Antigen-Mediated Toxin Entry
    description: >-
      Anthrax antitoxins neutralize protective antigen-dependent toxin entry
      upstream of lethal factor and edema factor cytosolic delivery.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      In animal models, treatment with the polyclonal or either monoclonal
      antitoxin provided a statistically significant (p<=0.0001for all three
      antitoxins) survival benefit compared with no treatment.
    explanation: >-
      CDC's systematic review found animal efficacy evidence for polyclonal
      AIGIV and the monoclonal antitoxins obiltoxaximab and raxibacumab.
  notes: >-
    Licensed antitoxin products include polyclonal anthrax immunoglobulin and
    monoclonal antibodies, so therapeutic_modality is recorded as OTHER rather
    than narrowing the whole class to MONOCLONAL_ANTIBODY.
- name: Postexposure Anthrax Vaccination
  description: >-
    Anthrax vaccination is paired with antimicrobial postexposure prophylaxis
    after exposure of an unvaccinated or incompletely vaccinated person so
    delayed spore germination can be covered after antimicrobial therapy stops.
  treatment_term:
    preferred_term: Vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  therapeutic_modality: VACCINE
  target_mechanisms:
  - target: Protective Antigen-Mediated Toxin Entry
    description: >-
      Human anthrax vaccines use protective antigen as the principal immunogen,
      priming antibody responses that neutralize protective antigen-dependent
      toxin entry if spores germinate after antibiotic prophylaxis ends.
    evidence:
    - reference: PMID:36980364
      reference_title: "Human Anthrax: Update of the Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Protective antigen is the principal protective immunogen in these
        licensed human vaccines
      explanation: >-
        Identifies protective antigen, the shared delivery component for lethal
        and edema toxins, as the immunogen targeted by licensed human vaccines.
  evidence:
  - reference: PMID:37963097
    reference_title: "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      For unvaccinated or incompletely vaccinated persons exposed to B. anthracis,
      PEP includes both antimicrobial drugs with activity against B. anthracis
      (PEPAbx) and anthrax vaccine (PEPVx).
    explanation: >-
      CDC guidelines pair antibiotic prophylaxis with vaccination after exposure
      in people who are not fully vaccinated.
📚

References & Deep Research

References

2
PMID:36980364
Human Anthrax: Update of the Diagnosis and Treatment.
No top-level findings curated for this source.
PMID:37963097
CDC Guidelines for the Prevention and Treatment of Anthrax, 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)

Create: Anthrax · 2026-09-25T03:32:16Z · View source

Created a first-pass Anthrax infectious-disease entry from the OpenScientist deep-research report and current CDC anthrax guidance. Added the B. anthracis infectious agent, portal-of-entry subtypes, zoonotic and spore-exposure transmission routes, a capsule/toxin-centered pathophysiology chain, cutaneous/inhalational/systemic/gastrointestinal phenotypes, and antibiotic, passive-antitoxin, and postexposure-vaccination treatments with exact-quote evidence.

OpenScientist ▸
Anthrax — Comprehensive Disease Characteristics Report
openscientist-autonomous 15 citations 2026-09-24T20:18:14.126295

Anthrax — Comprehensive Disease Characteristics Report

Disease: Anthrax MONDO ID: MONDO:0005119 Category: Infectious Disease (bacterial zoonosis) Causative agent: Bacillus anthracis (NCBI:txid1392)

Evidence-source note: Anthrax is an infectious/environmental disease, not a heritable human genetic disorder. Accordingly, sections framed around germline "causal genes," "pathogenic variants," "inheritance patterns," and "penetrance" of the human host are largely Not applicable; where genetics matters, it is (a) the pathogen's virulence genes/plasmids and (b) host receptor/immune genes influencing susceptibility. This is flagged throughout. Information is drawn from aggregated disease-level resources (CDC, WHO, OMIM/pathogen genomics, PubMed) rather than individual EHR patient records.

1. Disease Information

Overview. Anthrax is an acute bacterial zoonotic disease caused by the Gram-positive, spore-forming rod Bacillus anthracis. It principally affects herbivorous mammals (cattle, sheep, goats, wild ungulates); humans are incidental hosts infected by contact with infected animals, contaminated animal products (hides, wool, bone, meat), contaminated soil, or—rarely—deliberately released spores (bioterrorism). Disease manifests in four forms defined by the portal of entry: cutaneous, gastrointestinal, inhalational (pulmonary), and injectional. All forms can progress to systemic infection with bacteremia, toxemia, sepsis, and hemorrhagic meningitis (PMID: 38638828).

Key identifiers. - MONDO: 0005119 - ICD-11: 1B97 (Anthrax); ICD-10: A22 (A22.0 cutaneous, A22.1 pulmonary, A22.2 gastrointestinal, A22.7 anthrax sepsis, A22.8, A22.9) - MeSH: D000881 (Anthrax); Descriptor for organism Bacillus anthracis D001409 - SNOMED CT: 409498004 (Anthrax) - DOID: DOID:7427 - Pathogen taxonomy: Bacillus anthracis NCBI:txid1392 - OMIM/Orphanet: No human Mendelian OMIM entry (infectious disease). Orphanet does not list anthrax as a rare genetic disease; related host receptor gene disorder: Hyaline Fibromatosis Syndrome (ANTXR2/CMG2, OMIM 228600) — see §4.

Synonyms / alternative names. Malignant pustule / malignant carbuncle (cutaneous form); woolsorters' disease / ragpickers' disease (inhalational, occupational); splenic fever; charbon; milzbrand; Siberian ulcer; injectional anthrax (heroin-associated).

Data derivation. Disease-level aggregated resources and published case series/surveillance, not individual-patient EHR.

2. Etiology

Primary cause (infectious). Infection by Bacillus anthracis. Environmentally persistent endospores are the infectious particle; they germinate to toxin-producing vegetative bacilli once inside a host. Full virulence requires two plasmids: - pXO1 (~182 kb) — encodes the three toxin components pagA (protective antigen, PA), lef (lethal factor, LF), cya (edema factor, EF) and the master regulator atxA. - pXO2 (~95 kb) — encodes the poly-γ-D-glutamic acid (PGA) capsule biosynthesis operon capBCADE.

Loss of either plasmid attenuates virulence; pXO1/atxA is required for intracellular macrophage escape and survival, pXO2 capsule for anti-phagocytic immune evasion (PMID: 11207600; PMID: 16334217).

Risk factors (environmental / occupational — dominant). - Occupational contact with livestock and animal products: farmers, herders, veterinarians, butchers/abattoir workers, wool/hide/leather handlers, ("woolsorters"), bone-meal/tannery workers (PMID: 26720232 — cases concentrated in animal-husbandry workers and housewives with animal contact). - Consumption of undercooked meat from infected animals (gastrointestinal/oropharyngeal form) (PMID: 29912259). - Injection drug use with contaminated heroin (injectional anthrax — European outbreaks 2009–2010). - Residence/work in endemic agricultural regions with poor veterinary-public-health infrastructure; contact with historical animal burial sites; warm-season and post-flood/drought soil disturbance. - Laboratory exposure; intentional aerosol release (bioterrorism — e.g., 2001 U.S. "Amerithrax" letters; 1979 Sverdlovsk accidental release). - Age/sex: cases skew to working-age adults with occupational exposure; male predominance in many series (e.g., 63% male, mean age ~44 y; PMID: 26720232).

Host genetic susceptibility factors. Not a classical genetic disease, but host genetics modulate toxin susceptibility: polymorphisms/expression of the toxin receptors ANTXR1 (TEM8) and ANTXR2 (CMG2) and downstream immune-signaling genes affect cellular sensitivity. Post-translational regulation (S-acylation cycles) of CMG2 controls receptor maturation and toxin susceptibility in vivo (PMID: 42409807). Inbred mouse strains differ in Nlrp1b inflammasome alleles that determine macrophage sensitivity to lethal toxin (model-organism evidence).

Protective factors. - Environmental/behavioral: livestock vaccination, safe carcass disposal (no butchering of animals dying suddenly), thorough cooking of meat, PPE in at-risk occupations, decontamination of animal products. - Immunological/medical: prior vaccination (anti-PA antibody), post-exposure prophylaxis (antibiotics ± vaccine). - Host genetic: Nlrp1b-mediated inflammasome activation that triggers rapid pyroptosis of infected macrophages can be protective against lethal-toxin lethality in mice (context-dependent; model-organism evidence).

Gene–environment interaction. Spore exposure (environment) intersects with host receptor availability and inflammasome genotype (genetics): only germinated bacilli producing toxin cause disease, and the host's ANTXR2/CMG2 receptor density and Nlrp1b allele determine cellular outcome (toxicity vs pyroptotic clearance). Occupational exposure interacts with vaccination status to determine net risk.

3. Phenotypes

Cutaneous anthrax (~95% of natural human cases). Type: clinical signs / physical manifestation. - Painless, pruritic papule → vesicle → black necrotic eschar ("malignant pustule") surrounded by non-pitting gelatinous edema; regional lymphadenopathy; low-grade fever/malaise. Incubation ~1–7 days (mean ~4.8 d; PMID: 26720232). Lesions most common on exposed hands/fingers/arms/face. Severity mild–moderate if treated; case-fatality ~20% untreated, <1% treated. HPO: HP:0000988 (skin rash), HP:0200041 (skin ulcer), HP:0011124 (localized skin lesion), HP:0000969 (edema), HP:0002090 (fever), HP:0002716 (lymphadenopathy).

Inhalational anthrax (most lethal). Type: clinical signs + laboratory/imaging abnormalities. - Biphasic: nonspecific flu-like prodrome (fever, malaise, dry cough, myalgia) → fulminant phase with dyspnea, hypoxemia, hemorrhagic mediastinitis with widened mediastinum, pleural effusions, shock, meningitis. Progression subacute→fulminant over days; severity severe; historic mortality ~85–90%, ~45% with modern intensive care/antitoxin. HPO: HP:0002094 (dyspnea), HP:0002878 (respiratory failure), HP:0002090, HP:0100749 (chest pain), HP:0032263 (mediastinal mass/widening — pleural effusion HP:0002202).

Gastrointestinal / oropharyngeal anthrax. Type: clinical signs. - Fever, severe abdominal pain, nausea/vomiting, hematemesis, bloody diarrhea, ascites, mesenteric adenopathy; oropharyngeal variant: throat pain, dysphagia, neck edema, oral ulcers. Severe; mortality ~25–60%. HPO: HP:0002240 (hepatomegaly/ascites HP:0001541), HP:0002573 (hematochezia), HP:0002013 (vomiting), HP:0002027 (abdominal pain), HP:0025267 (nausea).

Injectional anthrax. Type: clinical signs. Deep soft-tissue/necrotizing infection at injection site, marked edema without classic eschar, high rate of sepsis; associated with contaminated heroin. HPO: HP:0100806 (sepsis), HP:0000969.

Systemic complications (any form). Anthrax sepsis/toxemia, hemorrhagic meningitis/meningoencephalitis (poor prognosis), shock, coagulopathy. HPO: HP:0100806 (sepsis), HP:0001287 (meningitis), HP:0002315 (headache), HP:0001259 (coma), HP:0011098 (seizure).

Quality-of-life impact. Acute, high-acuity illness; survivors of cutaneous form may have scarring/contractures from eschars on hands. Severe systemic disease causes ICU-level morbidity, respiratory failure, neurological sequelae in meningitis survivors. No chronic relapsing phenotype (disease is acute/self-limited if survived).

4. Genetic / Molecular Information

Human causal genes: Not applicable — anthrax is not inherited. There are no human germline "causal genes," pathogenic ACMG/AMP variants, allele frequencies, or somatic/germline classifications for the disease itself.

Pathogen virulence genes (the relevant "genetics"): | Gene | Plasmid | Product | Function | |------|---------|---------|----------| | pagA | pXO1 | Protective antigen (PA83) | Receptor binding + translocon; delivers LF/EF | | lef | pXO1 | Lethal factor (LF) | Zn²⁺-metalloprotease; cleaves MAPKKs (MEK1/2/3/4/6/7), NLRP1 | | cya | pXO1 | Edema factor (EF) | Calmodulin-dependent adenylate cyclase; ↑cAMP | | atxA | pXO1 | AtxA | Master trans-activator of toxin + capsule genes | | capBCADE | pXO2 | PGA capsule machinery | Poly-γ-D-glutamate anti-phagocytic capsule | | acpA/acpB | pXO2 | Capsule regulators | Capsule expression control |

Host genes relevant to susceptibility (host receptor / modifier genes): - ANTXR2 / CMG2 (HGNC:21036; OMIM 608041) — primary anthrax toxin entry receptor; also a Collagen VI receptor for ECM homeostasis. Its loss-of-function mutations cause Hyaline Fibromatosis Syndrome (OMIM 228600) — a distinct human genetic disorder, notable because it reveals CMG2's dual physiological role and its regulation by S-acylation cycles that also control toxin susceptibility (PMID: 42409807). - ANTXR1 / TEM8 (HGNC:21014; OMIM 606410) — secondary/alternative toxin receptor; LOF causes GAPO syndrome and infantile hemangioma susceptibility (host disorders, not anthrax). - NLRP1 (inflammasome; direct LF substrate in rodents) — determines macrophage pyroptosis vs toxicity; a susceptibility modifier (strong in mouse, human NLRP1 also LF-responsive).

Epigenetic / chromosomal features. Not applicable to human host disease. Pathogen genome: single circular chromosome (~5.2 Mb) plus pXO1/pXO2; near-clonal population structure; typed by canonical SNPs and MLVA/VNTR (e.g., TaqMan/canSNP assays, PMID: 33371332).

5. Environmental Information

  • Environmental reservoir: B. anthracis spores persist in soil for decades, favored by alkaline, calcium-rich soils and cycles of flooding/drought that concentrate spores; grazing animals ingest/inhale spores. Distribution modeling identifies host abundance, soil composition, climate, and vegetation as key determinants (PMID: 39509442).
  • Occupational exposures: hides, wool, hair, bone meal, contaminated meat (see §2).
  • Lifestyle factors: consumption of meat from animals that died suddenly; injection drug use.
  • Infectious agent: Bacillus anthracis (NCBI:txid1392); Family Bacillaceae. Closely related to B. cereus group; distinguished by pXO1/pXO2 and phenotype (non-motile, non-hemolytic, penicillin-susceptible, gamma-phage susceptible).

6. Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation)

  1. Spore entry through skin abrasion, ingestion, inhalation, or injection leads to deposition of dormant endospores in tissue.
  2. Spores are phagocytosed by local macrophages/dendritic cells and transported toward regional lymph nodes; germination-triggering signals (amino acids, nucleosides) result in germination to vegetative bacilli.
  3. Intracellular germinating bacilli, via pXO1/atxA-dependent functions, escape the phagosome and survive/replicate, then lyse and exit the macrophage (PMID: 11207600; PMID: 16334217).
  4. Extracellular vegetative bacilli express the pXO2 poly-γ-D-glutamate capsule, which inhibits phagocytosis and complement → immune evasion → unchecked bacteremia (can reach 10⁷–10⁸ CFU/mL).
  5. atxA activates toxin gene expression; PA83 binds host receptors ANTXR2/CMG2 (primary) and ANTXR1/TEM8 (PMID: 42409807).
  6. Cell-surface furin cleaves PA83 → PA63 (releasing PA20); PA63 oligomerizes into a heptamer/octamer prepore that binds up to 3–4 molecules of LF and/or EF (PMID: 42600039).
  7. Receptor-mediated endocytosis and endosomal acidification convert the prepore to a membrane-spanning pore (φ-clamp–gated translocase); LF and EF translocate into the cytosol.
  8. Branch A — Lethal toxin (PA+LF): LF (Zn-metalloprotease) cleaves MAPKKs (MEK1/2/3/4/6/7) and activates/cleaves NLRP1 → disrupts ERK/p38/JNK signaling → impairs dendritic cell & macrophage function, endothelial dysfunction, and (in sensitive cells) pyroptosis/apoptosis → immune paralysis, vascular barrier failure, hypotensive shock.
  9. Branch B — Edema toxin (PA+EF): EF (Ca²⁺/calmodulin-dependent adenylate cyclase) massively raises intracellular cAMP → fluid/electrolyte efflux and tissue edema, impaired neutrophil function, further immune suppression.
  10. Combined toxemia + bacteremia result in systemic inflammatory collapse: capillary leak, hemorrhage, hypoxia, DIC-like coagulopathy, multi-organ failure, and frequently hemorrhagic meningitis (bacterial/toxin CNS invasion) → death.

Upstream drivers = spore germination, plasmid-encoded capsule and toxins; downstream effectors = MAPKK cleavage, cAMP surge, endothelial/immune failure and shock. (Steps 8–9 branch and converge on step 10.)

Molecular pathways: MAPK/ERK, p38, JNK cascades (disrupted by LF); cAMP–PKA signaling (hyperactivated by EF); NLRP1 inflammasome; furin-mediated proprotein processing; receptor-mediated endocytosis. KEGG: ko05150-type bacterial pathways; Reactome anthrax-toxin entry. Cellular processes: phagocytosis, phagosomal escape, pyroptosis/apoptosis, inflammasome activation, endothelial barrier dysfunction, immune suppression. GO: GO:0006909 (phagocytosis), GO:0070269 (pyroptosis), GO:0006954 (inflammatory response), GO:0000165 (MAPK cascade), GO:0071356 (cellular response to cytokine). Protein dysfunction: host MAPKK proteolysis (loss of function of MEK signaling); pathological gain of adenylate-cyclase activity in cytosol; PA conformational activation/oligomerization is essential and drug-targetable (PMID: 42600039). Immune involvement: capsule-mediated anti-phagocytosis; toxin-mediated suppression of innate and adaptive immunity; cytokine dysregulation; late overwhelming sepsis. Tissue-damage mechanisms: hemorrhage, edema, necrosis, thrombosis, oxidative/ischemic injury from vascular collapse. GO/CL suggestions: biological processes GO:0006954, GO:0000165, GO:0070269; cell types CL:0000235 (macrophage), CL:0000451 (dendritic cell), CL:0000115 (endothelial cell), CL:0000775 (neutrophil).

7. Anatomical Structures Affected

  • Organ level (primary, by form): skin/dermis (cutaneous, UBERON:0002097 skin); lungs & mediastinal lymph nodes (inhalational — note primary lesion is hemorrhagic mediastinal lymphadenitis, not pneumonia; UBERON:0002048 lung, UBERON:0002509 mesenteric/UBERON:0000029 lymph node); GI tract — stomach/intestine/oropharynx (UBERON:0000160 intestine, UBERON:0000945 stomach).
  • Secondary / systemic: blood (bacteremia; UBERON:0000178), spleen (UBERON:0002106; "splenic fever"), meninges/brain (hemorrhagic meningitis; UBERON:0002360 meninges, UBERON:0000955 brain), liver, adrenal glands, cardiovascular system (shock).
  • Body systems: integumentary, respiratory, digestive, lymphatic/hematologic, cardiovascular, central nervous.
  • Tissue/cell level: dermal connective tissue and vascular endothelium; alveolar and lymphatic macrophages; dendritic cells. Cell Ontology: CL:0000235 (macrophage), CL:0000451 (dendritic cell), CL:0000115 (endothelial cell), CL:0000775 (neutrophil).
  • Subcellular: endosome/endolysosome (toxin translocation), plasma membrane (PA pore), cytosol (LF/EF targets), nucleus-linked MAPK signaling. GO CC: GO:0005768 (endosome), GO:0005886 (plasma membrane), GO:0005829 (cytosol).
  • Lateralization: cutaneous lesions typically unilateral/localized at inoculation site; systemic disease is diffuse/bilateral (e.g., bilateral pleural effusions, symmetric mediastinal widening).

8. Temporal Development

  • Onset: Incubation typically 1–7 days (cutaneous mean ~4.8 d, PMID: 26720232); inhalational usually 1–7 days but can be delayed weeks (spore dormancy — up to ~43 days observed at Sverdlovsk). Any age; occupational cases in working-age adults. Onset pattern: acute (cutaneous) to subacute→fulminant biphasic (inhalational).
  • Progression / stages: cutaneous — papule→vesicle→eschar over ~2–6 days, then healing over weeks. Inhalational — prodromal (flu-like) stage → fulminant systemic stage within 2–5 days; rapid deterioration once fulminant. Systemic sepsis/meningitis can kill within 24–72 h.
  • Course pattern: acute, self-limited if survived (no chronic/relapsing course); untreated systemic disease is rapidly progressive.
  • Remission: treatment-induced recovery with antibiotics ± antitoxin; cutaneous lesions heal with scar. No spontaneous chronic remission-relapse cycles.
  • Critical intervention window: outcome hinges on early antibiotic (and antitoxin) initiation before/at the fulminant toxemic phase; post-exposure prophylaxis is most effective before symptom onset.

9. Inheritance and Population (Epidemiology)

  • Inheritance: Not applicable (infectious disease; no Mendelian inheritance, penetrance, expressivity, anticipation, founder effect, carrier frequency, or consanguinity relevance for the host).
  • Global distribution: worldwide but endemic in agricultural regions of sub-Saharan Africa, Central & South Asia, the Middle East, southern/eastern Europe (e.g., Türkiye), the Caucasus, and parts of Central/South America; hyperendemic where livestock vaccination is limited. Modeled suitable zones include central/eastern Türkiye, Armenia, Georgia, southern Russia, Bulgaria, Romania, Hungary, Moldova (PMID: 39509442). Rare/sporadic in most high-income countries.
  • Incidence/prevalence: Human anthrax is rare and under-reported globally; WHO historically estimated on the order of thousands to ~tens of thousands of human cases per year worldwide, concentrated in endemic foci. It is a recognized but poorly quantified neglected zoonotic disease — prioritized in 65 countries yet with minimal formal burden estimates (PMID: 37545541). In endemic countries incidence is highly seasonal (warm months / post-rain) and occupational.
  • Demographics: male predominance and working-age adults in occupational series (e.g., 63% male, mean age ~44 y, cases peaking Aug–Sep; PMID: 26720232). No ethnic genetic predisposition; distribution reflects exposure.
  • Sex ratio: roughly male-skewed where occupational exposure dominates; broadly ~1:1–2:1 M:F by setting.

10. Diagnostics

  • Microbiology (gold standard): Gram stain (large Gram-positive rods in chains, "boxcar" morphology, unencapsulated in culture / encapsulated in tissue with polychrome methylene blue M'Fadyean reaction), culture on sheep-blood agar (non-hemolytic, non-motile, catalase-positive, "medusa-head"/ground-glass colonies), gamma-phage lysis and penicillin susceptibility for confirmation. Blood cultures positive in systemic disease.
  • Molecular: PCR/qPCR targeting plasmid markers (pagA/lef on pXO1, capB on pXO2) and chromosomal markers; multiplex TaqMan assays and canSNP/MLVA genotyping for strain typing (PMID: 33371332). Metagenomic next-generation sequencing (mNGS), including from FFPE tissue, can confirm difficult cases rapidly (PMID: 38638828).
  • Immunoassays / biomarkers: anti-PA IgG serology and toxin (PA/LF) detection assays (ELISA, mass-spectrometry LF activity assay — CDC); useful retrospectively and epidemiologically.
  • Histopathology: skin biopsy — necrosis, edema, hemorrhage, vasculitis, PAS-positive/encapsulated bacilli (PMID: 38638828); tissues show hemorrhagic lymphadenitis/mediastinitis.
  • Imaging: chest X-ray/CT — widened mediastinum, pleural effusions, hilar adenopathy (inhalational); abdominal imaging — ascites, bowel-wall edema (GI); CT/MRI + LP for hemorrhagic meningitis (CSF often hemorrhagic).
  • Diagnostic criteria: clinical + exposure history + laboratory confirmation per CDC/WHO case definitions (confirmed vs probable/suspect).
  • Differential diagnosis: cutaneous — spider bite, ecthyma gangrenosum, orf, tularemia, plague, staphylococcal/streptococcal cellulitis, rat-bite fever; inhalational — influenza, community-acquired pneumonia, mediastinitis, aortic dissection; GI — other bacterial gastroenteritis, acute abdomen.
  • Screening: environmental/animal surveillance; no routine human population screening (rare disease). Genetic testing: not applicable.

11. Outcome / Prognosis

  • Cutaneous: case-fatality ~20% untreated, <1% with antibiotics; excellent prognosis if treated early (PMID: 26720232 series: 1.2% mortality overall, the single death from meningitis).
  • Gastrointestinal: ~25–60% mortality depending on care/recognition.
  • Inhalational: historically ~85–90% mortality; ~45% with modern ICU care, combination antibiotics, and antitoxin (2001 U.S. outbreak: 5/11 inhalational cases died despite treatment).
  • Injectional: high morbidity/mortality (~30%+), often requiring surgical debridement.
  • Anthrax meningitis: near-uniformly fatal without aggressive therapy; a leading cause of death across forms.
  • Prognostic factors: clinical form and portal of entry; time to effective antibiotics/antitoxin; presence of meningitis, shock, pleural effusion; bacterial burden/toxemia; comorbidities. Early treatment before the fulminant toxemic phase is the strongest determinant of survival.
  • Morbidity/QoL: survivors of severe systemic disease may have prolonged ICU recovery, respiratory compromise, and neurological deficits (post-meningitis); cutaneous scarring/contractures.

12. Treatment

Antimicrobials (mainstay). - Fluoroquinolones: ciprofloxacin, levofloxacin (NCIT drug classes); first-line for treatment/PEP. - Tetracyclines: doxycycline (first-line PEP/treatment). - Beta-lactams: penicillin G / amoxicillin for penicillin-susceptible strains (naturally acquired often susceptible — PMID: 38638828 cured with IV penicillin; PMID: 26720232 penicillin group used in 78%); note intrinsic β-lactamase risk, so not for empiric bioterrorism use. - Others active: clindamycin, linezolid (add for toxin/protein-synthesis suppression and CNS penetration), meropenem, rifampin, vancomycin. - Systemic/meningitis regimens: CDC recommends ≥2–3 drug combination IV therapy including a bactericidal agent (fluoroquinolone) + a protein-synthesis inhibitor (linezolid/clindamycin) + CNS-penetrant agent when meningitis is possible. - Duration: systemic disease treated intravenously then oral; inhalational/post-exposure prophylaxis requires 60 days of oral antibiotics because of spore dormancy.

Antitoxins (adjuncts for systemic disease — target PA). - Raxibacumab — human anti-PA monoclonal antibody (FDA-approved 2012). - Obiltoxaximab (ETI-204) — anti-PA monoclonal (FDA-approved 2016). - Anthrax immune globulin (AIG, Anthrasil) — polyclonal anti-PA from vaccinated donors. These neutralize circulating toxin; used with antibiotics for systemic/severe anthrax. Next-generation ultrapotent anti-PA antibodies blocking PA63 oligomerization are in development (e.g., 22F1, IC50 = 0.027 nM; PMID: 42600039).

Supportive / interventional care: aggressive fluid/vasopressor support for shock, pleural fluid drainage (improves outcome by removing toxin-rich effusion), mechanical ventilation, surgical debridement (injectional/severe cutaneous — avoid excising uncomplicated eschars), corticosteroids for extensive head/neck edema or meningitis.

Pharmacogenomics: not a major factor; standard drug-metabolism considerations (e.g., CYP interactions with ciprofloxacin) apply. NCIT suggestions: Ciprofloxacin (C2778), Doxycycline (C459), Penicillin (C739), Raxibacumab (C82675), Obiltoxaximab, Linezolid, Clindamycin, Anthrax Immune Globulin.

13. Prevention

  • Primary prevention:
  • Animal vaccination (live attenuated Sterne strain, pXO1+/pXO2−) — cornerstone of control in livestock; reduces human exposure.
  • Human vaccination: AVA / BioThrax (Anthrax Vaccine Adsorbed, PA-based, adsorbed to aluminum hydroxide) and AV7909 (Cyfendus) (PA + CPG7909 adjuvant, approved for PEP). Recommended for at-risk occupations, certain military personnel, and lab workers. PA-based vaccines neutralize toxin but do not block spore germination/bacteremia, motivating multi-antigen and spore-antigen research (PMID: 18166249; PMID: 17005989).
  • Behavioral/occupational: PPE, safe handling/decontamination of animal products, proper carcass disposal (deep burial/incineration, no butchering of sudden-death animals), meat inspection, control of injection-drug spore contamination.
  • Secondary prevention: rapid case detection and post-exposure prophylaxis — 60 days antibiotics (ciprofloxacin/doxycycline) plus a 3-dose vaccine series after confirmed aerosol exposure; environmental surveillance and decontamination after release.
  • Tertiary prevention: early combination antibiotics + antitoxin to prevent progression to shock/meningitis; pleural drainage; ICU support.
  • Public health: One-Health surveillance linking veterinary and human health, outbreak investigation, environmental decontamination (formaldehyde/chlorine dioxide for spores), education of at-risk communities (PMID: 40303149 — KAP gaps in endemic Ethiopia), biosecurity/select-agent regulation to prevent misuse.
  • Genetic counseling: not applicable.

14. Other Species / Natural Disease

  • Taxonomy of hosts: primarily herbivorous mammals — cattle (Bos taurus, NCBI:txid9913), sheep (Ovis aries, txid9940), goats (Capra hircus, txid9925), horses (Equus caballus, txid9796), and wild ungulates (bison, deer, antelope, hippopotamus, elephants). Carnivores and omnivores (including humans, Homo sapiens txid9606) are more resistant and usually acquire via ingestion.
  • Natural disease / veterinary importance: anthrax is a major cause of sudden death in grazing livestock and wildlife, with peracute presentation (sudden death, incomplete rigor, dark unclotted blood from orifices, splenomegaly). Devastating wildlife die-offs occur (e.g., savanna herbivores, hippos). It is a notifiable/reportable OIE (WOAH) disease of high economic and food-security impact (PMID: 39509442; OMIA resources).
  • Comparative pathology: herbivores develop rapidly fatal septicemic anthrax; carnivores/humans show more localized/variable disease due to higher innate resistance — reflecting species differences in receptor biology and innate immunity (e.g., Nlrp1 inflammasome variation across species/strains).
  • Zoonotic transmission: all human cases derive from animals/animal products or environment; no significant human-to-human transmission (except rare cutaneous contact). Cross-species susceptibility is broad among mammals.

15. Model Organisms

  • Mice (Mus musculus, NCBI:txid10090): the workhorse model for toxin action, vaccine/antitoxin efficacy, and inflammasome biology; inbred strains differ in Nlrp1b alleles governing macrophage sensitivity to lethal toxin. Recapitulate toxemia/lethality; used for PA-vaccine protection studies (PMID: 18166249; PMID: 17005989). Limitation: strain-dependent toxin sensitivity; not all reproduce human inhalational mediastinitis.
  • Rats: classic model for edema/lethal toxin lethality (Fischer 344 rats highly sensitive to lethal toxin), useful for antitoxin pharmacology.
  • Rabbits (Oryctolagus cuniculus, txid9986) and non-human primates (rhesus/cynomolgus macaques, Macaca spp.): gold-standard inhalational anthrax models; closely mimic human disease (mediastinal lymphadenitis, toxemia, meningitis) and are the basis for FDA "Animal Rule" licensure of vaccines/antitoxins.
  • Guinea pigs: used for vaccine potency testing.
  • Zebrafish (Danio rerio, txid7955): used to study CMG2/anthrax-toxin receptor biology and S-acylation-dependent toxin susceptibility in vivo; APT2 inhibition attenuated toxin toxicity (PMID: 42409807).
  • Cellular / in vitro: J774A.1 and RAW264.7 macrophage lines for spore germination, intracellular survival, and pyroptosis assays (PMID: 11207600; PMID: 16334217); CHO and other lines for PA-pore translocation and receptor studies; engineered PA nanopores for biophysics (PMID: 42326671; PMID: 41520172).
  • Applications: toxin mechanism, receptor/translocation biology, vaccine and antitoxin efficacy, inflammasome/host-defense genetics, therapeutic screening.
  • Resources: MGI (mouse), RGD (rat), ZFIN (zebrafish), Cellosaurus/ATCC (cell lines); Alliance of Genome Resources.

Evidence-Source Legend

  • Human clinical: PMID 38638828, 26720232, 29912259, 36980364, 33371332, 39509442, 37545541, 40303149.
  • In vitro / molecular / structural: PMID 42600039, 42409807, 42326671, 41520172, 42124355, 11207600, 16334217.
  • Model organism / vaccine: PMID 18166249, 17005989, 42409807, 11207600.

Limitations

  • No primary dataset was provided; report synthesizes literature and canonical databases.
  • Global human burden is poorly quantified (neglected zoonosis; under-reporting).
  • Several therapeutic/mechanistic details (antitoxin approvals, CDC regimens, Animal Rule) rest on regulatory/guideline sources rather than the specific PMIDs retrievable in this session; PMIDs cited support the core mechanistic and clinical claims. Some retrieved records are recent structural/biophysical studies used to anchor the toxin-mechanism narrative.

Future Directions

  • Multi-antigen/spore-targeted vaccines that block germination and bacteremia (not only toxin).
  • Next-generation ultrapotent anti-PA antibodies (oligomerization blockers, PMID 42600039) and small-molecule translocation inhibitors.
  • Host-directed therapy exploiting receptor S-acylation cycles (PMID 42409807).
  • Improved One-Health surveillance and burden quantification in endemic regions.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome Count
References checked 15
Resolved 15
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 15
On topic 8
Off topic 0

All extracted references resolved successfully.

Term Validation

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

Outcome Count
Terms checked 48
Resolved 46
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 2
Terms whose name was checked 31
Terms named correctly 23
Terms named as a different term 5
Terms whose name is worth a second look 3

Terms the report names something else

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

  • MONDO:0005119 (2 mentions) - the report calls it "if available"; MONDO calls it anthrax infection
  • HP:0011124 (1 mention) - the report calls it "localized skin lesion"; HP calls it Abnormal epidermal morphology
  • HP:0002090 (2 mentions) - the report calls it "fever"; HP calls it Pneumonia
  • HP:0025267 (1 mention) - the report calls it "nausea"; HP calls it Snoring
  • HP:0011098 (1 mention) - the report calls it "seizure"; HP calls it Speech apraxia

Terms whose name is worth a second look

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

  • HP:0200041 (1 mention) - the report calls it "skin ulcer"; HP calls it Skin erosion
  • GO:0070269 (2 mentions) - the report calls it "pyroptosis"; GO calls it pyroptotic inflammatory response, and lists "pyroptosis" among its other names
  • GO:0071356 (1 mention) - the report calls it "cellular response to cytokine"; GO calls it cellular response to tumor necrosis factor, and lists "cellular response to TNF" among its other names