Plague is a severe zoonotic disease caused by the Gram-negative bacterium Yersinia pestis. Transmitted primarily by flea bites from infected rodent reservoirs, Y. pestis can manifest as bubonic, septicemic, or pneumonic plague. The bacterium deploys a type III secretion system to inject Yop effector proteins into host immune cells, suppressing phagocytosis and inflammatory responses. Without prompt antibiotic treatment, plague is frequently fatal, particularly in its pneumonic and septicemic forms. Historically, the Black Death pandemic of 1346-1353 killed an estimated 30-50% of the European population and exerted one of the strongest known selective pressures on the human genome, notably driving selection of immune-related variants such as the ERAP2 rs2549794 allele.
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name: Plague
creation_date: '2026-04-03T00:00:00Z'
category: Infectious Disease
description: >
Plague is a severe zoonotic disease caused by the Gram-negative bacterium
Yersinia pestis. Transmitted primarily by flea bites from infected rodent
reservoirs, Y. pestis can manifest as bubonic, septicemic, or pneumonic
plague. The bacterium deploys a type III secretion system to inject Yop
effector proteins into host immune cells, suppressing phagocytosis and
inflammatory responses. Without prompt antibiotic treatment, plague is
frequently fatal, particularly in its pneumonic and septicemic forms.
Historically, the Black Death pandemic of 1346-1353 killed an estimated
30-50% of the European population and exerted one of the strongest known
selective pressures on the human genome, notably driving selection of
immune-related variants such as the ERAP2 rs2549794 allele.
parents:
- Bacterial Infection
disease_term:
preferred_term: plague
term:
id: MONDO:0019095
label: plague
synonyms:
- Black Death
- Pestilence
- Pneumonic Plague
- Yersinia pestis infection
infectious_agent:
- name: Yersinia pestis
infectious_agent_term:
preferred_term: Yersinia pestis
term:
id: NCBITaxon:632
label: Yersinia pestis
evidence:
- reference: PMID:12951845
reference_title: "Yersinia pestis and the plague."
supports: SUPPORT
snippet: Yersinia pestis is the cause of plague, an illness that may manifest in bubonic, pneumonic, or septicemic form.
explanation: Establishes Y. pestis as the causative agent of all forms of plague.
agent_life_cycle:
description: >-
Yersinia pestis persists in enzootic sylvatic cycles between burrowing
rodents and their fleas, with mice, rats, prairie dogs and ground squirrels
among the hosts of established foci. Periodic epizootics kill off rodent
colonies, which raises human exposure. The flea acquires the bacterium in a
bloodmeal, a biofilm forms in the proventriculus, and a blocked flea
regurgitates bacteria into the next bite wound; blockage is most frequent in
the rat flea Xenopsylla cheopis. Humans are accidental hosts. Which small
rodents, if any, sustain the agent between epizootics is unsettled.
hosts:
- preferred_term: rats
role: Rodent host of the enzootic cycle in established plague foci
term:
id: NCBITaxon:10114
label: Rattus
- preferred_term: prairie dogs
role: >-
Burrowing rodent host; colonies suffer plague die-offs, the epizootic that
raises human risk
term:
id: NCBITaxon:45478
label: Cynomys
- preferred_term: Oriental rat flea
role: >-
Flea vector; proventricular blockage and regurgitative transmission are
most frequent in this species
term:
id: NCBITaxon:163159
label: Xenopsylla cheopis
- preferred_term: Homo sapiens
role: >-
Accidental host, infected by an infected flea; not part of the enzootic
cycle
term:
id: NCBITaxon:9606
label: Homo sapiens
vectors:
- Oriental rat flea (Xenopsylla cheopis)
- Other rodent fleas of the enzootic sylvatic cycle
life_cycle_stages:
- name: Enzootic sylvatic maintenance in burrowing rodents and their fleas
description: >-
Worldwide plague foci persist through a rodent-flea-rodent cycle among
burrowing rodents, which are the natural reservoirs of the agent.
evidence:
- reference: PMID:39179552
reference_title: Transovarial transmission of Yersinia pestis in its flea vector Xenopsylla cheopis.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: "Worldwide plague foci persist due to enzootic sylvatic cycles consisting of burrowing rodents and their respective flea vectors"
explanation: >-
States the enzootic cycle as the reason foci persist, naming burrowing
rodents and their fleas as its two components.
- reference: PMID:39179552
reference_title: Transovarial transmission of Yersinia pestis in its flea vector Xenopsylla cheopis.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: "Numerous flea species and primarily rodent hosts are implicated in maintaining the sylvatic plague cycle, with mice, rats, prairie dogs, and ground squirrels commonly found in established plague foci"
explanation: >-
Names the rodent hosts of established foci, including the rats and
prairie dogs bound above.
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: "Plague is a vector-borne illness transmitted by fleas to a variety of wildlife rodents, which represent natural reservoirs for the disease in a wide range of habitats around the world"
explanation: >-
Independently assigns the reservoir role to wildlife rodents and the
transmitting role to fleas.
- name: Epizootic amplification and rodent die-off
description: >-
Plague periodically sweeps through a rodent colony and kills it off. These
epizootics are what bring infected fleas into contact with people. Whether
any small rodent carries the agent between epizootics is disputed.
evidence:
- reference: PMID:18689662
reference_title: Exposure of small rodents to plague during epizootics in black-tailed prairie dogs.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
quote_role: BACKGROUND
snippet: "Plague, caused by the bacterium Yersinia pestis, causes die-offs of colonies of prairie dogs (Cynomys ludovicianus)."
explanation: >-
Establishes the epizootic die-off in prairie dog colonies, the host bound
above for this stage.
- reference: PMID:18689662
reference_title: Exposure of small rodents to plague during epizootics in black-tailed prairie dogs.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
quote_role: BACKGROUND
snippet: "It has been argued that other small rodents are reservoirs for plague, spreading disease during epizootics and maintaining the pathogen in the absence of prairie dogs; yet there is little empirical support for distinct enzootic and epizootic cycles."
explanation: >-
Records that the interepizootic maintenance host is proposed rather than
demonstrated, which is why no such host is bound here.
- name: Flea acquisition, proventricular blockage and transmission to humans
description: >-
A flea acquires the bacterium in a bloodmeal; a biofilm occludes the
proventriculus so that the blocked flea regurgitates bacteria into the
bite wound. Blockage occurs most often in the rat flea.
evidence:
- reference: PMID:39179552
reference_title: Transovarial transmission of Yersinia pestis in its flea vector Xenopsylla cheopis.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: "Blockage and transmission by blocked fleas was most frequent in the rat flea, Xenopsylla cheopis, with more than 50% occurrence"
explanation: >-
Quantifies blockage in the specific flea species bound as the principal
vector, which is the mechanism of the transmitting step.
evidence:
- reference: PMID:39179552
reference_title: Transovarial transmission of Yersinia pestis in its flea vector Xenopsylla cheopis.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: "Yersinia pestis, the causative agent of plague, is endemic in certain regions due to a stable transmission cycle between rodents and their associated fleas."
explanation: >-
Gives the overall two-component framework this block records: a stable
rodent-flea cycle that keeps the agent endemic.
has_subtypes:
- name: Bubonic
display_name: Bubonic Plague
curated_in: Bubonic_Plague
description: >
Most common form, resulting from flea bite inoculation. Y. pestis travels
to regional lymph nodes, causing painful swollen lymph nodes (buboes),
fever, and prostration. Without treatment, case fatality is approximately
40-60%. Curated as a standalone entry, Bubonic_Plague (MONDO:0001112),
which carries the flea-mediated inoculation to lymph-node colonization to
bubo mechanism.
evidence:
- reference: PMID:32435802
reference_title: "Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019."
supports: SUPPORT
snippet: Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively.
explanation: Confirms bubonic plague as the most common clinical form at 63% of cases.
- name: Septicemic
display_name: Septicemic Plague
curated_in: Septicemic_Plague
description: >
Bloodstream infection without prominent bubo formation, or secondary to
bubonic plague. Characterized by disseminated intravascular coagulation,
purpura, and multi-organ failure. Highest case fatality among treated
patients. Curated as a standalone entry, Septicemic_Plague (MONDO:0005956),
which carries the immune-evasion to bloodstream-infection to DIC mechanism.
evidence:
- reference: PMID:32435802
reference_title: "Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019."
supports: SUPPORT
snippet: Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively.
explanation: Septicemic plague accounts for approximately 5% of cases but carries the highest treated case fatality rate at 38%.
- name: Pneumonic
display_name: Pneumonic Plague
curated_in: Pneumonic_Plague
description: >
Infection of the lungs, either primary (from aerosol inhalation) or
secondary (hematogenous spread from bubo). Transmissible person-to-person
via respiratory droplets. Rapidly fatal without treatment within 48 hours.
Curated as a standalone entry, Pneumonic_Plague (MONDO:0001024), which
carries the inhaled-or-hematogenous lung seeding to exudative
bronchopneumonia mechanism.
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague)
explanation: Confirms the extreme lethality and rapid progression of pneumonic plague.
pathophysiology:
- name: Flea-Mediated Transmission
description: >
Y. pestis is transmitted to humans through the bite of an infected flea.
The bacterium colonizes the flea midgut and forms a biofilm that blocks
the proventriculus, causing the flea to regurgitate bacteria into the
bite wound during feeding attempts.
locations:
- preferred_term: Skin
term:
id: UBERON:0002097
label: skin of body
downstream:
- target: Type III Secretion System Deployment
description: >
After inoculation into the dermis, Y. pestis deploys its type III
secretion system upon contact with host immune cells.
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs, Y. pestis emerged <6000 years ago from an enteric bacterial ancestor through events of gene gain and genome reduction.
explanation: Establishes flea-mediated vector transmission as the primary route of Y. pestis infection.
- name: Type III Secretion System Deployment
description: >
Upon contact with host immune cells, Y. pestis deploys a type III
secretion system (T3SS) encoded on the pYV/pCD1 virulence plasmid. The
T3SS forms a needle-like injectisome that directly delivers Yop effector
proteins into the cytoplasm of target immune cells.
cell_types:
- preferred_term: Macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: Neutrophil
term:
id: CL:0000775
label: neutrophil
- preferred_term: Dendritic Cell
term:
id: CL:0000451
label: dendritic cell
downstream:
- target: Yop Effector Injection and Immune Subversion
description: >
The T3SS injects multiple Yop effector proteins that each target
distinct immune cell signaling pathways.
evidence:
- reference: PMID:24198067
reference_title: "The Yersinia pestis type III secretion system: expression, assembly and role in the evasion of host defenses."
supports: SUPPORT
snippet: Within the host cell, the Yop effector proteins function to inhibit bacterial phagocytosis and to suppress the production of pro-inflammatory cytokines.
explanation: Describes the T3SS-delivered Yop effectors and their functions within host cells.
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: A complex set of virulence determinants, including the Yersinia outer-membrane proteins (Yops), the broad-range protease Pla, pathogen-associated molecular patterns (PAMPs), and iron capture systems play critical roles in the molecular strategies that Y. pestis employs to subvert the human immune system
explanation: Confirms the multi-factorial virulence strategy including Yops and Pla protease.
- name: Yop Effector Injection and Immune Subversion
description: >
Individual Yop effector proteins target distinct immune cell functions.
YopH dephosphorylates focal adhesion proteins to block phagocytosis.
YopE and YopT inactivate Rho GTPases controlling cytoskeleton dynamics.
YopJ/YopP prevents NF-kappaB activation, suppressing pro-inflammatory
cytokine production.
biological_processes:
- preferred_term: Phagocytosis
term:
id: GO:0006909
label: phagocytosis
modifier: DECREASED
- preferred_term: Innate immune response
term:
id: GO:0045087
label: innate immune response
modifier: DECREASED
downstream:
- target: Phagocytosis Inhibition and Bacterial Replication
description: >
Combined Yop-mediated suppression of phagocytosis allows unrestricted
extracellular bacterial replication.
evidence:
- reference: PMID:10922034
reference_title: "Molecular and cell biology aspects of plague."
supports: SUPPORT
snippet: YopH is a powerful phosphotyrosine phosphatase playing an antiphagocytic role by dephosphorylating several focal adhesion proteins. YopE and YopT contribute to antiphagocytic effects by inactivating GTPases controlling cytoskeleton dynamics. YopP/YopJ plays an anti-inflammatory role by preventing the activation of the transcription factor NF-kappaB.
explanation: Details the specific molecular mechanisms of each Yop effector in immune evasion.
evidence_source: IN_VITRO
- name: Phagocytosis Inhibition and Bacterial Replication
description: >
The combined effect of Yop-mediated immune subversion is that
macrophages and neutrophils cannot effectively engulf and kill Y. pestis.
This allows unrestricted extracellular bacterial replication at the
inoculation site, enabling dissemination to draining lymph nodes.
biological_processes:
- preferred_term: Defense response to Gram-negative bacterium
term:
id: GO:0050829
label: defense response to Gram-negative bacterium
modifier: DECREASED
downstream:
- target: Lymph Node Colonization and Bubo Formation
description: >
Bacteria disseminate from the inoculation site via lymphatics to
regional lymph nodes, where they replicate massively.
- name: Lymph Node Colonization and Bubo Formation
description: >
After immune evasion at the inoculation site, Y. pestis disseminates to
draining lymph nodes where it replicates massively, causing the
characteristic painful swollen lymph nodes (buboes) that define bubonic
plague.
cell_types:
- preferred_term: Macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: Neutrophil
term:
id: CL:0000775
label: neutrophil
biological_processes:
- preferred_term: Inflammatory response
term:
id: GO:0006954
label: inflammatory response
locations:
- preferred_term: Lymph node
term:
id: UBERON:0000029
label: lymph node
downstream:
- target: Systemic Spread and Septicemic Plague
description: >
Bacteria can escape from lymph nodes into the bloodstream, causing
septicemia, disseminated intravascular coagulation, and multi-organ
failure.
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: allowing unrestricted bacterial replication in lymph nodes (bubonic plague) and in lungs (pneumonic plague)
explanation: Confirms that lymph nodes are a primary site of Y. pestis replication in bubonic plague.
- reference: PMID:12951845
reference_title: "Yersinia pestis and the plague."
supports: SUPPORT
snippet: Yersinia pestis is the cause of plague, an illness that may manifest in bubonic, pneumonic, or septicemic form. Plague has killed an estimated 200 million humans throughout history
explanation: Establishes that bubonic form involves lymph node involvement and that plague has been historically devastating.
- name: Systemic Spread and Septicemic Plague
description: >
When Y. pestis enters the bloodstream from infected lymph nodes or
directly, it causes septicemia with disseminated intravascular
coagulation, purpura (historically giving the disease its 'Black Death'
name), and multi-organ failure.
cell_types:
- preferred_term: Monocyte
term:
id: CL:0000576
label: monocyte
biological_processes:
- preferred_term: Inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
- preferred_term: Apoptotic process
term:
id: GO:0006915
label: apoptotic process
modifier: INCREASED
downstream:
- target: Pneumonic Plague
description: >
Hematogenous spread to the lungs can cause secondary pneumonic plague.
evidence:
- reference: PMID:10922034
reference_title: "Molecular and cell biology aspects of plague."
supports: SUPPORT
snippet: "YopP/YopJ plays an anti-inflammatory role by preventing the activation of the transcription factor NF-kappaB. It also induces rapid apoptosis of macrophages."
explanation: Yop-mediated macrophage apoptosis contributes to uncontrolled bacterial dissemination and systemic disease.
evidence_source: IN_VITRO
- reference: PMID:15207311
reference_title: "Plague."
supports: SUPPORT
snippet: Bubonic disease, pneumonic plague, and septicemic plague are seen in addition to a number of other less common manifestations.
explanation: Confirms the clinical spectrum including septicemic plague.
- name: Pneumonic Plague
description: >
Lung infection with Y. pestis, arising either from hematogenous spread
(secondary) or direct inhalation of infectious respiratory droplets
(primary). Pneumonic plague is characterized by fulminant pneumonia,
hemoptysis, and respiratory failure. It is the only form transmissible
person-to-person and is nearly 100% fatal without early antibiotic
treatment.
cell_types:
- preferred_term: Macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: Neutrophil
term:
id: CL:0000775
label: neutrophil
biological_processes:
- preferred_term: Innate immune response
term:
id: GO:0045087
label: innate immune response
modifier: DECREASED
- preferred_term: Inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
locations:
- preferred_term: Lung
term:
id: UBERON:0002048
label: lung
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague)
explanation: Confirms the extreme lethality and rapidity of pneumonic plague without treatment.
- reference: PMID:24198067
reference_title: "The Yersinia pestis type III secretion system: expression, assembly and role in the evasion of host defenses."
supports: SUPPORT
snippet: Yersinia pestis, the etiologic agent of plague, utilizes a type III secretion system (T3SS) to subvert the defenses of its mammalian hosts.
explanation: T3SS-mediated immune evasion applies to pulmonary infection as well.
- name: ERAP2 Evolutionary Selection
description: >
The Black Death pandemic of 1346-1353 exerted powerful selective pressure
on the human genome, particularly at immune loci. The rs2549794 variant
in ERAP2 was strongly selected, as the allele producing a full-length
ERAP2 transcript conferred improved ability to control intracellular
Y. pestis in macrophages. This same protective allele is now associated
with increased susceptibility to autoimmune diseases, representing a
classic case of antagonistic pleiotropy shaped by past pandemic selection.
biological_processes:
- preferred_term: Immune response
term:
id: GO:0006955
label: immune response
- preferred_term: Proteolysis
term:
id: GO:0006508
label: proteolysis
notes: >
ERAP2 encodes an endoplasmic reticulum aminopeptidase involved in
antigen processing for MHC class I presentation. The selected haplotype B
produces a full-length functional protein, while the alternative produces
a truncated, non-functional transcript.
evidence:
- reference: PMID:36261521
reference_title: "Evolution of immune genes is associated with the Black Death."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages.
explanation: Directly demonstrates that ERAP2 rs2549794 was selected during the Black Death and confers functional immune advantage against Y. pestis.
- reference: PMID:36261521
reference_title: "Evolution of immune genes is associated with the Black Death."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.
explanation: Demonstrates antagonistic pleiotropy where plague-protective alleles now increase autoimmune disease risk.
phenotypes:
- name: Bubo (Lymphadenopathy)
category: Signs and Symptoms
description: >
Painful, swollen lymph nodes (buboes) in the inguinal, axillary, or
cervical region, characteristic of bubonic plague.
subtype: Bubonic
notes: >
Painful swollen lymph nodes (buboes) are the defining feature of bubonic
plague; cited abstracts mention "bubonic disease" by name but do not
describe the lymphadenopathy in their text.
phenotype_term:
preferred_term: Bubo (swollen lymph node)
term:
id: HP:0002716
label: Lymphadenopathy
- name: Fever
category: Signs and Symptoms
description: High fever, often with rigors, accompanying all forms of plague.
notes: >
Fever is a cardinal presenting feature of all forms of plague; cited
abstracts do not explicitly name it in their text.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
- name: Purpura
category: Signs and Symptoms
description: >
Skin hemorrhages (purpura and ecchymoses) resulting from disseminated
intravascular coagulation in septicemic plague, historically responsible
for the name 'Black Death'.
subtype: Septicemic
phenotype_term:
preferred_term: Purpura
term:
id: HP:0000979
label: Purpura
- name: Disseminated Intravascular Coagulation
category: Signs and Symptoms
description: >
Consumption coagulopathy with simultaneous thrombosis and hemorrhage,
a hallmark of septicemic plague leading to multi-organ failure.
subtype: Septicemic
phenotype_term:
preferred_term: Disseminated intravascular coagulation
term:
id: HP:0005521
label: Disseminated intravascular coagulation
- name: Pneumonia
category: Signs and Symptoms
description: >
Fulminant pneumonia with bloody sputum (hemoptysis), dyspnea, and
rapid respiratory failure in pneumonic plague.
subtype: Pneumonic
phenotype_term:
preferred_term: Pneumonia
term:
id: HP:0002090
label: Pneumonia
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: allowing unrestricted bacterial replication in lymph nodes (bubonic plague) and in lungs (pneumonic plague)
explanation: Confirms lung involvement as a primary site in pneumonic plague.
- name: Dyspnea
category: Signs and Symptoms
description: Shortness of breath, especially in pneumonic plague.
subtype: Pneumonic
phenotype_term:
preferred_term: Dyspnea
term:
id: HP:0002094
label: Dyspnea
- name: Cough
category: Signs and Symptoms
description: Cough, often productive with bloody sputum, in pneumonic plague.
subtype: Pneumonic
phenotype_term:
preferred_term: Cough
term:
id: HP:0012735
label: Cough
- name: Sepsis
category: Signs and Symptoms
description: Systemic bacterial infection with organ dysfunction.
subtype: Septicemic
phenotype_term:
preferred_term: Sepsis
term:
id: HP:0100806
label: Sepsis
- name: Splenomegaly
category: Signs and Symptoms
description: Enlargement of spleen from systemic infection.
phenotype_term:
preferred_term: Splenomegaly
term:
id: HP:0001744
label: Splenomegaly
- name: Chest Pain
category: Signs and Symptoms
description: Pleuritic chest pain accompanying pneumonic plague.
subtype: Pneumonic
phenotype_term:
preferred_term: Chest pain
term:
id: HP:0100749
label: Chest pain
genetic:
- name: ERAP2
association: Evolutionary selection during Black Death
gene_term:
preferred_term: ERAP2
term:
id: hgnc:29499
label: ERAP2
notes: >
The rs2549794 variant near ERAP2 was strongly selected during the
1346-1353 Black Death pandemic. The selected allele produces a
full-length ERAP2 aminopeptidase that enhances control of intracellular
Y. pestis in macrophages through improved antigen processing. This
protective allele is now associated with increased susceptibility to
autoimmune diseases (antagonistic pleiotropy).
evidence:
- reference: PMID:36261521
reference_title: "Evolution of immune genes is associated with the Black Death."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages.
explanation: ERAP2 rs2549794 was under positive selection during the Black Death and provides functional immune advantage.
treatments:
- name: Aminoglycoside Antibiotics
description: >
Streptomycin and gentamicin are first-line treatments for plague.
Aminoglycosides have the longest track record of efficacy against
Y. pestis infection.
treatment_term:
preferred_term: aminoglycoside antibiotic therapy
term:
id: NCIT:C15620
label: Antibiotic Therapy
evidence:
- reference: PMID:32435802
reference_title: "Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019."
supports: SUPPORT
snippet: Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects.
explanation: Confirms aminoglycosides as effective first-line treatment for plague.
- reference: PMID:32435800
reference_title: "Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939-2019."
supports: SUPPORT
snippet: Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague.
explanation: Aggregate data confirms aminoglycosides among the most effective treatments for plague.
- name: Tetracycline Antibiotics
description: >
Doxycycline and other tetracyclines are effective alternatives for
plague treatment and prophylaxis. Used when aminoglycosides are
contraindicated.
treatment_term:
preferred_term: tetracycline antibiotic therapy
term:
id: NCIT:C15620
label: Antibiotic Therapy
evidence:
- reference: PMID:32435800
reference_title: "Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939-2019."
supports: SUPPORT
snippet: Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague.
explanation: Confirms tetracyclines among the most effective plague treatments.
- name: Supportive Care
description: >
Intensive supportive care including fluid resuscitation, vasopressor
support, and management of DIC complications for severe septicemic
and pneumonic plague.
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
transmission:
- name: Flea-borne Transmission
description: >
Primary route of plague transmission. Infected fleas (primarily Xenopsylla
cheopis, the Oriental rat flea) transmit Y. pestis to humans during blood
meals. The bacterium forms a biofilm in the flea's proventriculus, which
is regurgitated during feeding.
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs
explanation: Confirms the flea-borne vector transmission route from rodent reservoirs.
- name: Respiratory Droplet Transmission
description: >
Person-to-person transmission occurs via respiratory droplets from
patients with pneumonic plague. This is the only form of plague that
can spread directly between humans.
notes: >
Person-to-person respiratory droplet transmission is a defining feature
of pneumonic plague; this is textbook knowledge not directly quoted in
the abstract cache of cited references.
- name: Direct Contact
description: >
Handling infected animals or tissues, particularly during skinning or
butchering of infected rodents or other mammals.
prevalence:
- population: Global
measure_type: ANNUAL_INCIDENCE
prevalence_class: BELOW_1_IN_1000000
notes: >
Approximately 2,000 cases reported annually to the WHO worldwide (a global
annual case count, not a point prevalence; ~0.25 cases per million people).
Endemic foci in Africa, Asia, and the Americas concentrate the burden well
above the global rate. Madagascar, Democratic Republic of Congo, and Peru
report the majority of modern cases.
evidence:
- reference: PMID:12951845
reference_title: "Yersinia pestis and the plague."
supports: SUPPORT
snippet: Approximately 2,000 cases of plague are reported each year to the World Health Organization, and concern has been raised about the possible use of Y pestis as an agent of bioterrorism.
explanation: Confirms approximately 2,000 annual cases reported globally.
progression:
- phase: Onset
incubation_days: 1-7
notes: >
Incubation period is typically 1-7 days for bubonic plague (usually 2-6
days) and 1-3 days for pneumonic plague. Onset is acute with sudden
fever, chills, and malaise.
- phase: Acute
notes: >
Rapid progression to bubo formation (bubonic), septicemia, or
pneumonia depending on clinical form. Without treatment, pneumonic
plague is fatal within 48 hours and bubonic plague within a week.
evidence:
- reference: PMID:30940874
reference_title: "Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics."
supports: SUPPORT
snippet: the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague)
explanation: Confirms the timeline of untreated plague progression.
- phase: Resolution or Death
notes: >
With prompt antibiotic treatment, most patients recover. Without
treatment, case fatality approaches 100% for pneumonic and septicemic
forms. Even with treatment, overall case fatality is approximately 20%.
evidence:
- reference: PMID:32435802
reference_title: "Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019."
supports: SUPPORT
snippet: The case fatality rate was 20% overall.
explanation: Confirms 20% overall case fatality even with treatment.
notes: >-
The Black Death pandemic (1346-1353) is the single greatest mortality event
in recorded history, killing 30-50% of the European population. Ancient DNA
studies have confirmed Y. pestis as the causative agent and revealed that
plague lineages were already circulating in Neolithic Europe thousands of
years before the Black Death. Y. pestis evolved from the enteric pathogen
Yersinia pseudotuberculosis less than 6,000 years ago through gene gain and
genome reduction events.