Trench Fever

Infectious Disease MONDO:0005991 Pathograph 17 Show in embeddings browser Bacterial Infection Vector-borne disease

Trench fever is a louse-borne Bartonella quintana infection transmitted when feces from infected human body lice contaminate broken skin. B. quintana colonizes erythrocytes to produce persistent bacteremia and a spectrum that includes endocarditis, chronic lymphadenopathy, and, especially in immunocompromised hosts, vasoproliferative bacillary angiomatosis.

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8
Pathophys.
7
Phenotypes
17
Pathograph
1
Medical Actions
1
Deep Research
🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES
⚙

Pathophysiology

8
Body-Louse Fecal Bartonella Inoculation
Infectious B. quintana shed in human-body-louse feces reaches a new host through contaminated bite scratches or other skin abrasions.
symbiont entry into host GO:0044409 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased symbiont entry into host (GO:0044409). GO:0044409 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Trw-Associated Erythrocyte Colonization Host entry gives B. quintana access to the bloodstream, where Bartonella Trw type IV secretion machinery supports erythrocyte tropism.
Show evidence (1 reference)
PMID:35803580 SUPPORT Model Organism
"Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria."
Supports fecal inoculation from the body louse as the initiating exposure.
Trw-Associated Erythrocyte Colonization
The Bartonella Trw type IV secretion system contributes to host-specific adhesion to erythrocytes, supporting the long-lasting intraerythrocytic bacteremia that characterizes B. quintana infection.
erythrocyte CL:0000232 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves erythrocyte (CL:0000232). CL:0000232 is a cell type from the Cell Ontology.
symbiont entry into host cell GO:0046718 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased symbiont entry into host cell (GO:0046718). GO:0046718 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Acute Febrile Bacteremic Illness Intraerythrocytic bacteremia produces the acute, often relapsing febrile illness that is the cardinal trench-fever syndrome.
Chronic Bacteremia and Endocarditis Persistent B. quintana bacteremia can remain chronic and seed blood-culture-negative bacterial endocarditis.
Show evidence (1 reference)
PMID:20548954 SUPPORT Model Organism
"The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes."
Bartonella mutagenesis and erythrocyte-assay data identify Trw as the lineage virulence factor that mediates erythrocyte adhesion, the red-cell colonization step curated here for B. quintana.
Acute Febrile Bacteremic Illness
The classic trench-fever syndrome is an acute bacteremic illness with sudden headache, pain in the shins, and high fever; a relapsing form with a shorter initial period and frequent relapses (the "five-day"/quintan periodicity) was also described.
erythrocyte CL:0000232 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves erythrocyte (CL:0000232). CL:0000232 is a cell type from the Cell Ontology.
Downstream
Fever The acute bacteremic illness produces high fever.
Headache The acute syndrome produces headache.
Bone pain The acute syndrome produces characteristic shin (tibial) bone pain.
Show evidence (2 references)
PMID:16494745 SUPPORT REVIEW SYNTHESIS Human Clinical
"The first was characterized by a sudden onset of headache, dizziness, pain in the shins, and elevated temperature"
Describes the classic acute trench-fever syndrome of headache, shin pain, and fever.
PMID:16494745 SUPPORT REVIEW SYNTHESIS Human Clinical
"The second manifestation of the disease was characterized by a shorter initial period and frequent relapses."
Describes the relapsing (five-day/quintan) form of trench fever.
Chronic Bacteremia and Endocarditis
Long-lasting B. quintana bacteremia is the systemic reservoir that produces chronic bacteremia and can seed Bartonella blood-culture-negative endocarditis.
biological process involved in interaction with host GO:0051701 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased biological process involved in interaction with host (GO:0051701). GO:0051701 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Chronic Bacteremia Persistent blood infection is the defining manifestation of this branch.
Bacterial Endocarditis Chronic bacteremia can seed bacterial endocarditis.
Chronic Lymphadenopathy Chronic B. quintana infection can produce chronic lymphadenopathy.
Vomp-Mediated Endothelial Adherence Circulating B. quintana adheres to vascular endothelium, the step that precedes the vasoproliferative branch.
Show evidence (1 reference)
PMID:16494745 SUPPORT Other
"It is now recognized as a reemerging pathogen among homeless populations in cities in the United States and Europe and is responsible for a wide spectrum of conditions, including chronic bacteremia, endocarditis, and bacillary angiomatosis."
The review supports chronic bacteremia and endocarditis as core systemic B. quintana manifestations.
Vomp-Mediated Endothelial Adherence
Variably expressed outer membrane proteins (Vomps), the trimeric autotransporter adhesins of B. quintana, mediate adherence to extracellular matrix and endothelial cells, the adhesion step upstream of the pro-angiogenic endothelial response.
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
BafA-Driven Endothelial VEGF Signaling Endothelial adherence positions B. quintana to drive the BafA/VEGF pro-angiogenic response.
Show evidence (2 references)
PMID:21536788 SUPPORT In Vitro
"Under static conditions, ECM adherence of B. henselae, B. quintana, and Y. enterocolitica was strongly dependent on the expression of their particular TAAs."
B. quintana ECM adherence was strongly dependent on its trimeric autotransporter adhesins (Vomps), the adhesion step this node captures.
PMID:21536788 SUPPORT BACKGROUND In Vitro
"Trimeric autotransporter adhesins (TAAs) are important virulence factors of Gram-negative bacteria responsible for adherence to extracellular matrix (ECM) and host cells."
Background on the trimeric-autotransporter-adhesin class to which the B. quintana Vomps belong.
BafA-Driven Endothelial VEGF Signaling
Bartonella BafA acts as a VEGF receptor 2 ligand; the B. quintana BafA homolog is functional, supporting a homologous pro-angiogenic route into endothelial proliferation in B. quintana-associated bacillary angiomatosis.
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.
positive regulation of angiogenesis GO:0045766 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased positive regulation of angiogenesis (GO:0045766). GO:0045766 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Bacillary Angiomatosis Pro-angiogenic endothelial signaling is a molecular route into vasoproliferative bacillary angiomatosis.
Show evidence (2 references)
PMID:32678094 SUPPORT In Vitro
"BafA interacts with vascular endothelial growth factor (VEGF) receptor-2 and activates the downstream signaling pathway, suggesting that BafA functions as a VEGF analog."
Identifies the Bartonella autotransporter mechanism that activates VEGFR2 signaling and drives endothelial angiogenic responses.
PMID:32678094 SUPPORT In Vitro
"A BafA homolog from a related pathogen, Bartonella quintana, is also functional."
Extends the BafA functional observation to the B. quintana homolog.
Bartonella Intracellular Persistence
B. quintana is an intracellular Bartonella pathogen; residence inside host cells constrains treatment toward cell-penetrant antimicrobials such as doxycycline.
Biological Process Involved in Interaction with Host GO:0051701 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Biological Process Involved in Interaction with Host (GO:0051701). GO:0051701 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:18611821 SUPPORT Other
"The intracellular location of some microorganisms allow them to resist antibiotics with poor ability to penetrate eukaryotic cell membranes, such as the beta-lactam compounds."
Review evidence for the intracellular-niche principle behind cell-penetrant antimicrobial selection.
Bartonella Ribosomal Translation
B. quintana depends on bacterial 70S ribosomal translation; doxycycline and gentamicin both act on the bacterial 30S ribosomal subunit.
translation GO:0006412 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves translation (GO:0006412). GO:0006412 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:24336183 SUPPORT Other
"The ribosome is one of the main antibiotic targets in the bacterial cell."
Review establishing the bacterial ribosome as the target of protein-synthesis inhibitors, the drug-target node represented here.
⬡

Pathograph

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

Phenotypes

7
Cardiovascular 2
Bacterial Endocarditis HP:0006689 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bacterial endocarditis (HP:0006689). HP:0006689 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15891120 SUPPORT Human Clinical
"Bartonella quintana is a fastidious microorganism associated with blood culture negative endocarditis."
Human endocarditis serology/PCR study identifies B. quintana as a blood-culture-negative endocarditis organism.
Chronic Lymphadenopathy HP:0002716 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lymphadenopathy (HP:0002716), qualified as temporality chronic. HP:0002716 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:8727894 SUPPORT Human Clinical
"Chronic adenomegaly in seronegative patients is a new clinical entity due to B. quintana."
Human case evidence supports chronic adenomegaly as a lymphadenopathy presentation of B. quintana infection.
Metabolism 2
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16494745 SUPPORT REVIEW SYNTHESIS Human Clinical
"The first was characterized by a sudden onset of headache, dizziness, pain in the shins, and elevated temperature"
Elevated temperature (fever) is a cardinal acute trench-fever feature.
Chronic Bacteremia HP:0031864 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bacteremia (HP:0031864). HP:0031864 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12821469 SUPPORT Human Clinical
"Chronic Bartonella quintana bacteremia is known to occur in homeless people exposed to lice."
Human trial report establishes chronic B. quintana bacteremia as a clinical manifestation after louse exposure.
Nervous System 1
Headache HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16494745 SUPPORT REVIEW SYNTHESIS Human Clinical
"The first was characterized by a sudden onset of headache, dizziness, pain in the shins, and elevated temperature"
Sudden headache is part of the acute trench-fever syndrome.
Constitutional 1
Bone pain HP:0002653 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Shin (tibial) bone pain, annotated with Bone pain (HP:0002653). HP:0002653 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16494745 SUPPORT REVIEW SYNTHESIS Human Clinical
"The first was characterized by a sudden onset of headache, dizziness, pain in the shins, and elevated temperature"
Pain in the shins is the characteristic tibial bone pain of trench fever.
Other 1
Bacillary Angiomatosis
Show evidence (1 reference)
PMID:9407154 SUPPORT Human Clinical
"Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent) were infected with B. henselae and 23 (47 percent) with B. quintana."
Human molecular epidemiology identifies B. quintana in nearly half of a bacillary angiomatosis-peliosis cohort.
💊

Medical Actions

1
Doxycycline Plus Gentamicin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: doxycycline CHEBI:50845 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses doxycycline (CHEBI:50845). CHEBI:50845 is a therapeutic agent from Chemical Entities of Biological Interest. gentamicin CHEBI:759884 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses gentamicin (CHEBI:759884). CHEBI:759884 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Combination therapy with doxycycline and gentamicin eradicates chronic B. quintana bacteremia in randomized-trial data.
Mechanism Target:
Bartonella Intracellular Persistence — Doxycycline has intracellular activity suited to Bartonella organisms in host-cell niches.
Bartonella Ribosomal Translation — Doxycycline and gentamicin inhibit bacterial ribosomal protein synthesis.
Show evidence (2 references)
PMID:12821469 SUPPORT Human Clinical
"This study demonstrates the efficiency of the combination of doxycycline and gentamicin in eradicating B. quintana bacteremia."
Randomized trial evidence supports doxycycline plus gentamicin for chronic B. quintana bacteremia.
PMID:23602630 SUPPORT Other
"In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate."
Systematic-review evidence independently supports this combination for chronic Bartonella bacteremia.
🌍

Environmental Factors

1
Body louse infestation and homelessness
Human body louse infestation - associated with homelessness, poverty, and poor hygiene - is the environmental context that supplies the louse vector for B. quintana, and urban trench fever is a reemerging disease of homeless populations.
Show evidence (2 references)
PMID:16494745 SUPPORT Other
"It is now recognized as a reemerging pathogen among homeless populations in cities in the United States and Europe"
Establishes homelessness/louse infestation as the reemergence context for trench fever.
PMID:16494745 SUPPORT Other
"which lives in clothes (Figure 2) and is associated with poverty, lack of hygiene, and cold weather"
The body louse vector is associated with poverty, poor hygiene, and cold weather.
Mechanism Target:
PREDISPOSES Body-Louse Fecal Bartonella Inoculation — Louse infestation in homeless, impoverished settings supplies the body-louse vector whose infectious feces inoculate B. quintana.
Show evidence (1 reference)
PMID:16494745 SUPPORT Other
"It is now recognized as a reemerging pathogen among homeless populations in cities in the United States and Europe"
B. quintana is a reemerging pathogen of homeless populations, the louse-infested context.
🔬

Diagnosis

1
Serology and PCR for blood-culture-negative endocarditis
Because B. quintana is fastidious and blood-culture-negative, diagnosis relies on serology and molecular detection (nested PCR of target genes) rather than routine culture.
serology and nested PCR for Bartonella NCIT:C17003 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:15891120 SUPPORT Human Clinical
"These sera were also positive by LightCycler nested PCR amplification for the rnpb (7 of 13) and fur (11 of 13) genes."
Nested PCR of the rnpB and fur genes on sera confirmed B. quintana in culture-negative endocarditis.
📈

Progression

2
Body-louse exposure and fecal inoculation
Infectious louse feces contaminate abrasions or scratch excoriations after body-louse feeding, initiating human B. quintana infection.
Show evidence (1 reference)
PMID:35803580 SUPPORT Model Organism
"Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria."
Supports infectious-feces exposure as the host-entry phase.
Persistent bacteremia and systemic complications
After host entry, B. quintana can establish intraerythrocytic bacteremia and cause chronic bacteremia, culture-negative endocarditis, and vasoproliferative bacillary angiomatosis.
Show evidence (1 reference)
PMID:16494745 SUPPORT Other
"It is now recognized as a reemerging pathogen among homeless populations in cities in the United States and Europe and is responsible for a wide spectrum of conditions, including chronic bacteremia, endocarditis, and bacillary angiomatosis."
The review summarizes the principal chronic and vasoproliferative clinical complications of B. quintana infection.
📊

Prevalence

1
Homeless people, Marseilles
Point Prevalence 5300.0 per 100,000 >1 in 1,000
B. quintana bacteremia was detected in 5.3% of 930 homeless people in Marseilles; the disease is concentrated in, not rare within, this cohort.
Show evidence (1 reference)
PMID:15643300 SUPPORT Human Clinical
"Bartonella quintana was isolated from blood culture in 50 patients (5.3%), 36 of whom were treated effectively"
B. quintana bacteremia was found in 5.3% of a 930-person homeless cohort.
🦠

Infectious Agent

1
Bartonella quintana
Human-restricted, louse-vectored Gram-negative Bartonella species that causes trench fever, chronic bacteremia, endocarditis, and bacillary angiomatosis.
Bartonella quintana NCBITaxon:803 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:16494745 SUPPORT Other
"Bartonella quintana, a pathogen that is restricted to human hosts and louse vectors, was first characterized as the agent of trench fever."
This review identifies B. quintana as the human- and louse-associated bacterial agent of trench fever.
↔️

Transmission

1
Body louse fecal transmission
The human body louse acquires B. quintana during blood feeding on a bacteremic person and passes infectious feces that can be scratched into broken skin of a new human host.
Show evidence (1 reference)
PMID:35803580 SUPPORT Model Organism
"Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria."
Body-louse infection experiments describe feces-mediated horizontal transmission as the route to humans.
{ }

Source YAML

click to show 
name: Trench Fever
creation_date: '2026-09-25T00:00:00Z'
category: Infectious Disease
description: >-
  Trench fever is a louse-borne Bartonella quintana infection transmitted when
  feces from infected human body lice contaminate broken skin. B. quintana
  colonizes erythrocytes to produce persistent bacteremia and a spectrum that
  includes endocarditis, chronic lymphadenopathy, and, especially in
  immunocompromised hosts, vasoproliferative bacillary angiomatosis.
disease_term:
  preferred_term: trench fever
  term:
    id: MONDO:0005991
    label: trench fever
parents:
- Bacterial Infection
- Vector-borne disease
synonyms:
- Five-day fever
- Quintan fever
- Shin bone fever
- His-Werner disease
- Wolhynia fever
- Urban trench fever
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
infectious_agent:
- name: Bartonella quintana
  description: >-
    Human-restricted, louse-vectored Gram-negative Bartonella species that causes
    trench fever, chronic bacteremia, endocarditis, and bacillary angiomatosis.
  infectious_agent_term:
    preferred_term: Bartonella quintana
    term:
      id: NCBITaxon:803
      label: Bartonella quintana
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bartonella quintana, a pathogen that is restricted to human hosts and louse
      vectors, was first characterized as the agent of trench fever.
    explanation: >-
      This review identifies B. quintana as the human- and louse-associated
      bacterial agent of trench fever.
transmission:
- name: Body louse fecal transmission
  description: >-
    The human body louse acquires B. quintana during blood feeding on a
    bacteremic person and passes infectious feces that can be scratched into
    broken skin of a new human host.
  evidence:
  - reference: PMID:35803580
    reference_title: >-
      Examination of vertical transmission of Bartonella quintana in body lice
      following multiple infectious blood meals.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Horizontal transmission from the body louse vector (Pediculus humanus
      humanus) to a human host occurs through contact with infectious louse feces
      containing a high concentration of the bacteria.
    explanation: >-
      Body-louse infection experiments describe feces-mediated horizontal
      transmission as the route to humans.
environmental:
- name: Body louse infestation and homelessness
  description: >-
    Human body louse infestation - associated with homelessness, poverty, and
    poor hygiene - is the environmental context that supplies
    the louse vector for B. quintana, and urban trench fever is a reemerging
    disease of homeless populations.
  influences_mechanisms:
  - target: Body-Louse Fecal Bartonella Inoculation
    environmental_effect: PREDISPOSES
    causal_link_type: DIRECT
    description: >-
      Louse infestation in homeless, impoverished settings supplies the body-louse
      vector whose infectious feces inoculate B. quintana.
    evidence:
    - reference: PMID:16494745
      reference_title: Bartonella quintana characteristics and clinical management.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        It is now recognized as a reemerging pathogen among homeless populations
        in cities in the United States and Europe
      explanation: B. quintana is a reemerging pathogen of homeless populations, the louse-infested context.
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now recognized as a reemerging pathogen among homeless populations
      in cities in the United States and Europe
    explanation: Establishes homelessness/louse infestation as the reemergence context for trench fever.
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      which lives in clothes (Figure 2) and is associated with poverty, lack of
      hygiene, and cold weather
    explanation: The body louse vector is associated with poverty, poor hygiene, and cold weather.
progression:
- phase: Body-louse exposure and fecal inoculation
  notes: >-
    Infectious louse feces contaminate abrasions or scratch excoriations after
    body-louse feeding, initiating human B. quintana infection.
  evidence:
  - reference: PMID:35803580
    reference_title: >-
      Examination of vertical transmission of Bartonella quintana in body lice
      following multiple infectious blood meals.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Horizontal transmission from the body louse vector (Pediculus humanus
      humanus) to a human host occurs through contact with infectious louse feces
      containing a high concentration of the bacteria.
    explanation: >-
      Supports infectious-feces exposure as the host-entry phase.
- phase: Persistent bacteremia and systemic complications
  notes: >-
    After host entry, B. quintana can establish intraerythrocytic bacteremia and
    cause chronic bacteremia, culture-negative endocarditis, and
    vasoproliferative bacillary angiomatosis.
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now recognized as a reemerging pathogen among homeless populations in
      cities in the United States and Europe and is responsible for a wide
      spectrum of conditions, including chronic bacteremia, endocarditis, and
      bacillary angiomatosis.
    explanation: >-
      The review summarizes the principal chronic and vasoproliferative clinical
      complications of B. quintana infection.
pathophysiology:
- name: Body-Louse Fecal Bartonella Inoculation
  description: >-
    Infectious B. quintana shed in human-body-louse feces reaches a new host
    through contaminated bite scratches or other skin abrasions.
  role: trigger
  biological_processes:
  - preferred_term: symbiont entry into host
    modifier: INCREASED
    term:
      id: GO:0044409
      label: symbiont entry into host
  evidence:
  - reference: PMID:35803580
    reference_title: >-
      Examination of vertical transmission of Bartonella quintana in body lice
      following multiple infectious blood meals.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Horizontal transmission from the body louse vector (Pediculus humanus
      humanus) to a human host occurs through contact with infectious louse feces
      containing a high concentration of the bacteria.
    explanation: >-
      Supports fecal inoculation from the body louse as the initiating exposure.
  downstream:
  - target: Trw-Associated Erythrocyte Colonization
    description: >-
      Host entry gives B. quintana access to the bloodstream, where Bartonella
      Trw type IV secretion machinery supports erythrocyte tropism.
- name: Trw-Associated Erythrocyte Colonization
  description: >-
    The Bartonella Trw type IV secretion system contributes to host-specific
    adhesion to erythrocytes, supporting the long-lasting intraerythrocytic
    bacteremia that characterizes B. quintana infection.
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  biological_processes:
  - preferred_term: symbiont entry into host cell
    modifier: INCREASED
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  evidence:
  - reference: PMID:20548954
    reference_title: >-
      The Trw type IV secretion system of Bartonella mediates host-specific
      adhesion to erythrocytes.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The corresponding genes encode components of the type IV secretion system
      (T4SS) Trw, demonstrating that this virulence factor laterally acquired by
      the Bartonella lineage is directly involved in adherence to erythrocytes.
    explanation: >-
      Bartonella mutagenesis and erythrocyte-assay data identify Trw as the
      lineage virulence factor that mediates erythrocyte adhesion, the red-cell
      colonization step curated here for B. quintana.
  downstream:
  - target: Acute Febrile Bacteremic Illness
    description: >-
      Intraerythrocytic bacteremia produces the acute, often relapsing febrile
      illness that is the cardinal trench-fever syndrome.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Chronic Bacteremia and Endocarditis
    description: >-
      Persistent B. quintana bacteremia can remain chronic and seed
      blood-culture-negative bacterial endocarditis.
- name: Acute Febrile Bacteremic Illness
  description: >-
    The classic trench-fever syndrome is an acute bacteremic illness with sudden
    headache, pain in the shins, and high fever; a relapsing form with a shorter
    initial period and frequent relapses (the "five-day"/quintan periodicity)
    was also described.
  role: consequence
  cell_types:
  - preferred_term: erythrocyte
    term:
      id: CL:0000232
      label: erythrocyte
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first was characterized by a sudden onset of headache, dizziness, pain
      in the shins, and elevated temperature
    explanation: Describes the classic acute trench-fever syndrome of headache, shin pain, and fever.
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The second manifestation of the disease was characterized by a shorter
      initial period and frequent relapses.
    explanation: Describes the relapsing (five-day/quintan) form of trench fever.
  downstream:
  - target: Fever
    description: The acute bacteremic illness produces high fever.
  - target: Headache
    description: The acute syndrome produces headache.
  - target: Bone pain
    description: The acute syndrome produces characteristic shin (tibial) bone pain.
- name: Chronic Bacteremia and Endocarditis
  description: >-
    Long-lasting B. quintana bacteremia is the systemic reservoir that produces
    chronic bacteremia and can seed Bartonella blood-culture-negative
    endocarditis.
  biological_processes:
  - preferred_term: biological process involved in interaction with host
    modifier: INCREASED
    term:
      id: GO:0051701
      label: biological process involved in interaction with host
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now recognized as a reemerging pathogen among homeless populations in
      cities in the United States and Europe and is responsible for a wide
      spectrum of conditions, including chronic bacteremia, endocarditis, and
      bacillary angiomatosis.
    explanation: >-
      The review supports chronic bacteremia and endocarditis as core systemic
      B. quintana manifestations.
  downstream:
  - target: Chronic Bacteremia
    description: Persistent blood infection is the defining manifestation of this branch.
  - target: Bacterial Endocarditis
    description: Chronic bacteremia can seed bacterial endocarditis.
  - target: Chronic Lymphadenopathy
    description: Chronic B. quintana infection can produce chronic lymphadenopathy.
  - target: Vomp-Mediated Endothelial Adherence
    description: >-
      Circulating B. quintana adheres to vascular endothelium, the step that
      precedes the vasoproliferative branch.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Vomp-Mediated Endothelial Adherence
  description: >-
    Variably expressed outer membrane proteins (Vomps), the trimeric
    autotransporter adhesins of B. quintana, mediate adherence to extracellular
    matrix and endothelial cells, the adhesion step upstream of the
    pro-angiogenic endothelial response.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  evidence:
  - reference: PMID:21536788
    reference_title: "Trimeric autotransporter adhesin-dependent adherence of Bartonella henselae, Bartonella quintana, and Yersinia enterocolitica to matrix components and endothelial cells under static and dynamic flow conditions."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Under static conditions, ECM adherence of B. henselae, B. quintana, and Y.
      enterocolitica was strongly dependent on the expression of their particular
      TAAs.
    explanation: >-
      B. quintana ECM adherence was strongly dependent on its trimeric
      autotransporter adhesins (Vomps), the adhesion step this node captures.
  - reference: PMID:21536788
    reference_title: "Trimeric autotransporter adhesin-dependent adherence of Bartonella henselae, Bartonella quintana, and Yersinia enterocolitica to matrix components and endothelial cells under static and dynamic flow conditions."
    supports: SUPPORT
    evidence_source: IN_VITRO
    quote_role: BACKGROUND
    snippet: >-
      Trimeric autotransporter adhesins (TAAs) are important virulence factors of
      Gram-negative bacteria responsible for adherence to extracellular matrix
      (ECM) and host cells.
    explanation: >-
      Background on the trimeric-autotransporter-adhesin class to which the B.
      quintana Vomps belong.
  downstream:
  - target: BafA-Driven Endothelial VEGF Signaling
    description: >-
      Endothelial adherence positions B. quintana to drive the BafA/VEGF
      pro-angiogenic response.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: BafA-Driven Endothelial VEGF Signaling
  description: >-
    Bartonella BafA acts as a VEGF receptor 2 ligand; the B. quintana BafA
    homolog is functional, supporting a homologous pro-angiogenic route into
    endothelial proliferation in B. quintana-associated bacillary angiomatosis.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: positive regulation of angiogenesis
    modifier: INCREASED
    term:
      id: GO:0045766
      label: positive regulation of angiogenesis
  evidence:
  - reference: PMID:32678094
    reference_title: >-
      The Bartonella autotransporter BafA activates the host VEGF pathway to
      drive angiogenesis.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      BafA interacts with vascular endothelial growth factor (VEGF) receptor-2
      and activates the downstream signaling pathway, suggesting that BafA
      functions as a VEGF analog.
    explanation: >-
      Identifies the Bartonella autotransporter mechanism that activates VEGFR2
      signaling and drives endothelial angiogenic responses.
  - reference: PMID:32678094
    reference_title: >-
      The Bartonella autotransporter BafA activates the host VEGF pathway to
      drive angiogenesis.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      A BafA homolog from a related pathogen, Bartonella quintana, is also
      functional.
    explanation: >-
      Extends the BafA functional observation to the B. quintana homolog.
  downstream:
  - target: Bacillary Angiomatosis
    description: >-
      Pro-angiogenic endothelial signaling is a molecular route into
      vasoproliferative bacillary angiomatosis.
    evidence:
    - reference: PMID:9407154
      reference_title: >-
        Molecular epidemiology of bartonella infections in patients with
        bacillary angiomatosis-peliosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent)
        were infected with B. henselae and 23 (47 percent) with B. quintana.
      explanation: >-
        Human molecular epidemiology connects B. quintana infection with
        bacillary angiomatosis-peliosis lesions.
- name: Bartonella Intracellular Persistence
  description: >-
    B. quintana is an intracellular Bartonella pathogen; residence inside host
    cells constrains treatment toward cell-penetrant antimicrobials such as
    doxycycline.
  role: intrinsic_resistance
  conforms_to: "intracellular_pathogen_persistence#Intracellular Niche and Beta-Lactam Exclusion"
  biological_processes:
  - preferred_term: Biological Process Involved in Interaction with Host
    term:
      id: GO:0051701
      label: biological process involved in interaction with host
  evidence:
  - reference: PMID:18611821
    reference_title: Intracellular organisms.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The intracellular location of some microorganisms allow them to resist
      antibiotics with poor ability to penetrate eukaryotic cell membranes, such
      as the beta-lactam compounds.
    explanation: >-
      Review evidence for the intracellular-niche principle behind
      cell-penetrant antimicrobial selection.
- name: Bartonella Ribosomal Translation
  description: >-
    B. quintana depends on bacterial 70S ribosomal translation; doxycycline and
    gentamicin both act on the bacterial 30S ribosomal subunit.
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:24336183
    reference_title: Ribosome-targeting antibiotics and mechanisms of bacterial resistance.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The ribosome is one of the main antibiotic targets in the bacterial cell.
    explanation: >-
      Review establishing the bacterial ribosome as the target of
      protein-synthesis inhibitors, the drug-target node represented here.
phenotypes:
- name: Fever
  description: >-
    High fever is the cardinal feature of the acute trench-fever syndrome,
    classically with a relapsing five-day (quintan) periodicity.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first was characterized by a sudden onset of headache, dizziness, pain
      in the shins, and elevated temperature
    explanation: Elevated temperature (fever) is a cardinal acute trench-fever feature.
- name: Headache
  description: Sudden-onset headache is part of the acute trench-fever syndrome.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first was characterized by a sudden onset of headache, dizziness, pain
      in the shins, and elevated temperature
    explanation: Sudden headache is part of the acute trench-fever syndrome.
- name: Bone pain
  description: >-
    Pain in the shins (tibial bone pain) is the classic musculoskeletal feature
    that gives trench fever the name "shin bone fever".
  phenotype_term:
    preferred_term: Shin (tibial) bone pain
    term:
      id: HP:0002653
      label: Bone pain
  evidence:
  - reference: PMID:16494745
    reference_title: Bartonella quintana characteristics and clinical management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first was characterized by a sudden onset of headache, dizziness, pain
      in the shins, and elevated temperature
    explanation: Pain in the shins is the characteristic tibial bone pain of trench fever.
- name: Chronic Bacteremia
  description: B. quintana can cause persistent blood infection.
  phenotype_term:
    preferred_term: Bacteremia
    term:
      id: HP:0031864
      label: Bacteremia
  evidence:
  - reference: PMID:12821469
    reference_title: >-
      Randomized open trial of gentamicin and doxycycline for eradication of
      Bartonella quintana from blood in patients with chronic bacteremia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Chronic Bartonella quintana bacteremia is known to occur in homeless
      people exposed to lice.
    explanation: >-
      Human trial report establishes chronic B. quintana bacteremia as a
      clinical manifestation after louse exposure.
- name: Bacterial Endocarditis
  description: >-
    B. quintana is an important cause of blood-culture-negative bacterial
    endocarditis.
  phenotype_term:
    preferred_term: Bacterial endocarditis
    term:
      id: HP:0006689
      label: Bacterial endocarditis
  evidence:
  - reference: PMID:15891120
    reference_title: High prevalence of Bartonella quintana endocarditis in Sfax, Tunisia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bartonella quintana is a fastidious microorganism associated with blood
      culture negative endocarditis.
    explanation: >-
      Human endocarditis serology/PCR study identifies B. quintana as a
      blood-culture-negative endocarditis organism.
- name: Chronic Lymphadenopathy
  description: >-
    Chronic adenomegaly or lymphadenopathy can occur with B. quintana infection,
    including in seronegative disease.
  phenotype_term:
    preferred_term: Lymphadenopathy
    temporality: CHRONIC
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:8727894
    reference_title: Bartonella (Rochalimaea) quintana infection in a seronegative hemodialyzed patient.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Chronic adenomegaly in seronegative patients is a new clinical entity due
      to B. quintana.
    explanation: >-
      Human case evidence supports chronic adenomegaly as a lymphadenopathy
      presentation of B. quintana infection.
- name: Bacillary Angiomatosis
  description: >-
    B. quintana is one molecularly typed cause of bacillary
    angiomatosis-peliosis in immunocompromised patients. No HP term for
    bacillary angiomatosis exists (OLS HP search "l~angiomatosis" returns only
    cystic angiomatosis of bone and visceral angiomatosis, neither of which
    fits), so no phenotype_term is bound.
  evidence:
  - reference: PMID:9407154
    reference_title: >-
      Molecular epidemiology of bartonella infections in patients with bacillary
      angiomatosis-peliosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent)
      were infected with B. henselae and 23 (47 percent) with B. quintana.
    explanation: >-
      Human molecular epidemiology identifies B. quintana in nearly half of a
      bacillary angiomatosis-peliosis cohort.
diagnosis:
- name: Serology and PCR for blood-culture-negative endocarditis
  description: >-
    Because B. quintana is fastidious and blood-culture-negative, diagnosis
    relies on serology and molecular detection (nested PCR of target genes)
    rather than routine culture.
  diagnosis_term:
    preferred_term: serology and nested PCR for Bartonella
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  evidence:
  - reference: PMID:15891120
    reference_title: High prevalence of Bartonella quintana endocarditis in Sfax, Tunisia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      These sera were also positive by LightCycler nested PCR amplification for
      the rnpb (7 of 13) and fur (11 of 13) genes.
    explanation: Nested PCR of the rnpB and fur genes on sera confirmed B. quintana in culture-negative endocarditis.
prevalence:
- population: Homeless people, Marseilles
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 5300.0
  notes: >-
    B. quintana bacteremia was detected in 5.3% of 930 homeless people in
    Marseilles; the disease is concentrated in, not rare within, this cohort.
  evidence:
  - reference: PMID:15643300
    reference_title: "Ectoparasitism and vector-borne diseases in 930 homeless people from Marseilles."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bartonella quintana was isolated from blood culture in 50 patients (5.3%),
      36 of whom were treated effectively
    explanation: B. quintana bacteremia was found in 5.3% of a 930-person homeless cohort.
treatments:
- name: Doxycycline Plus Gentamicin
  description: >-
    Combination therapy with doxycycline and gentamicin eradicates chronic
    B. quintana bacteremia in randomized-trial data.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
    - preferred_term: gentamicin
      term:
        id: CHEBI:759884
        label: gentamicin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Bartonella Intracellular Persistence
    description: >-
      Doxycycline has intracellular activity suited to Bartonella organisms in
      host-cell niches.
  - target: Bartonella Ribosomal Translation
    description: >-
      Doxycycline and gentamicin inhibit bacterial ribosomal protein synthesis.
  evidence:
  - reference: PMID:12821469
    reference_title: >-
      Randomized open trial of gentamicin and doxycycline for eradication of
      Bartonella quintana from blood in patients with chronic bacteremia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study demonstrates the efficiency of the combination of doxycycline
      and gentamicin in eradicating B. quintana bacteremia.
    explanation: >-
      Randomized trial evidence supports doxycycline plus gentamicin for chronic
      B. quintana bacteremia.
  - reference: PMID:23602630
    reference_title: "Treatment outcomes of human bartonellosis: a systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In chronic bacteremia, gentamicin and doxycycline significantly increased
      the resolution rate.
    explanation: >-
      Systematic-review evidence independently supports this combination for
      chronic Bartonella bacteremia.
📚

References & Deep Research

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Create: Trench Fever · 2026-09-25T07:03:33Z · View source

Created a Trench Fever infectious-disease entry grounded in an OpenScientist deep-research report for MONDO:0005991. Added Bartonella quintana as the infectious agent, body-louse fecal transmission, progression phases, erythrocyte-colonization and vasoproliferative pathophysiology, chronic bacteremia/endocarditis/lymphadenopathy/bacillary angiomatosis phenotypes, and doxycycline plus gentamicin pharmacotherapy targeting intracellular persistence and bacterial ribosomal translation. Verified the deep-research report with preflight-dr before curation, resolved ontology bindings through OAK/validate-terms, copied reference titles from cache frontmatter, and validated exact snippets against cached PMID records.

OpenScientist ▸
Trench Fever (Bartonella quintana infection): A Comprehensive Disease Characteristics Report
openscientist-autonomous 19 citations 2026-09-24T23:52:10.896049

Trench Fever (Bartonella quintana infection): A Comprehensive Disease Characteristics Report

Disease: Trench Fever · MONDO ID: MONDO:0005991 · Category: Infectious Disease Causal agent: Bartonella quintana (α-proteobacteria; formerly Rochalimaea quintana) ICD-10: A79.0 · ICD-11: 1C30.0 · MeSH: D014205 (Trench Fever) Evidence base: aggregated disease-level literature (reviews, case-control studies, one randomized trial, experimental microbiology). No individual EHR or genomic data files were provided; this report synthesizes primary literature retrieved via PubMed (27 papers reviewed, 11 findings confirmed).

Summary

Trench fever is a louse-borne bacterial infection caused by Bartonella quintana, a small, fastidious, facultatively intracellular α-proteobacterium that is restricted to a single natural reservoir — humans — and a single principal vector, the human body louse (Pediculus humanus humanus). First characterized in 1915 among soldiers in the trenches of World War I (hence the name), the disease has re-emerged over the past three decades as "urban trench fever" among homeless and socially marginalized populations in high-income cities in the US and Europe (PMID: 16494745). It is fundamentally a disease of poverty and body-louse infestation, not a genetic disease; there are no known human causal genes, susceptibility loci, or heritable risk factors.

Clinically, B. quintana produces a broad spectrum running from the classic self-limited relapsing febrile illness ("five-day fever," with headache and severe shin/tibial bone pain) through chronic afebrile bacteremia, blood-culture-negative endocarditis, chronic lymphadenopathy, and — particularly in immunocompromised hosts such as people with HIV — the vasoproliferative disorders bacillary angiomatosis and peliosis (PMID: 16494745; PMID: 15891120). Two mechanistic axes dominate the pathophysiology: (1) the laterally acquired Trw type IV secretion system (T4SS) mediates host-specific adhesion to and invasion of erythrocytes, producing the hallmark long-lasting intraerythrocytic bacteremia; and (2) a suite of factors — the Vomps trimeric autotransporter adhesins, the VirB/VirD4 T4SS with its Bep effectors, and the BafA autotransporter (a VEGF analog) — converge on HIF-1/VEGF signaling to drive endothelial proliferation, tube formation, and angiogenesis (PMID: 20548954; PMID: 32678094; PMID: 21536788; PMID: 23163798).

Diagnosis rests on serology, blood culture (often prolonged), and molecular detection (PCR of gltA/ftsZ/16S rRNA). The best-supported treatment for chronic bacteremia is doxycycline plus gentamicin, validated by a randomized open trial (eradication in 7/7 per-protocol treated vs 2/9 controls, P=0.003) (PMID: 12821469) and a systematic review/meta-analysis (PMID: 23602630). Prevention is fundamentally body-louse control and improved hygiene/social conditions; there is no vaccine. This report synthesizes 11 confirmed findings across all 15 template sections.

Key Findings

Finding 1 — Trench fever is caused by Bartonella quintana, a human-restricted, louse-borne pathogen

Bartonella quintana is an α-proteobacterium (formerly Rochalimaea quintana) whose lifestyle is restricted to human hosts and louse vectors. It was the first Bartonella species definitively linked to human disease and was characterized as the agent of trench fever, a disease "described in 1915 on the basis of natural and experimental infections in soldiers" (PMID: 16494745). After decades of relative obscurity, it re-emerged as a pathogen of the urban homeless: in a study of homeless persons, B. quintana was isolated from blood culture in 5.3% of patients (PMID: 15643300).

The verbatim evidence: "Bartonella quintana, a pathogen that is restricted to human hosts and louse vectors, was first characterized as the agent of trench fever. The disease was described in 1915 on the basis of natural and experimental infections in soldiers" (PMID: 16494745).

Key identifiers: MONDO:0005991; ICD-10 A79.0; ICD-11 1C30.0; MeSH D014205. This is an infectious, aggregated disease-level entity — knowledge is derived from case series, cohort studies, microbiology, and molecular biology, not from Mendelian/EHR genetic resources (no OMIM/Orphanet gene entry applies because it is not heritable). Common synonyms: five-day fever, quintan fever, His-Werner disease, shin bone fever, wolhynia fever, urban trench fever.

Finding 2 — B. quintana causes a clinical spectrum from classic trench fever to chronic bacteremia, endocarditis, and bacillary angiomatosis

B. quintana is "responsible for a wide spectrum of conditions, including chronic bacteremia, endocarditis, and bacillary angiomatosis" (PMID: 16494745). The classic acute syndrome is a relapsing fever recurring at ~5-day intervals ("quintana" = fifth), with headache, dizziness, and characteristic severe pain in the shins/tibiae. Beyond the acute illness, chronic afebrile bacteremia can persist for months; endocarditis is an important severe outcome. In a series from Sfax, Tunisia, B. quintana endocarditis "represents 9.8% of all endocarditis" in that setting, with high IgG titers (≥1:800) supporting the diagnosis (PMID: 15891120). Chronic infection can also present as isolated lymphadenopathy/adenomegaly, including in seronegative patients (PMID: 8727894). In immunocompromised hosts (notably HIV), the organism drives vasoproliferative disease — bacillary angiomatosis and peliosis.

Clinical syndrome Host context Key features HPO/phenotype terms
Classic trench fever Immunocompetent Relapsing 5-day fever, headache, severe shin/bone pain Fever HP:0001945; Headache HP:0002315; Bone pain HP:0002653
Chronic afebrile bacteremia Homeless, louse-exposed Persistent intraerythrocytic bacteremia Bacteremia HP:0031864
Blood-culture-negative endocarditis Valvulopathy/chronic infection Vegetations, high IgG titers; may need valve surgery Endocarditis HP:0100584
Chronic lymphadenopathy Sometimes seronegative Adenomegaly Lymphadenopathy HP:0002716
Bacillary angiomatosis / peliosis Immunocompromised (HIV) Vasoproliferative skin/bone/visceral lesions Cutaneous vascular lesions

Finding 3 — Trw T4SS mediates erythrocyte invasion; BafA drives VEGF-dependent angiogenesis

Two experimentally demonstrated virulence mechanisms anchor the pathophysiology.

(1) Erythrocyte invasion via the Trw T4SS. Using signature-tagged mutagenesis in surrogate Bartonella species, the Trw type IV secretion system was shown to be directly involved in erythrocyte adhesion; its genes "encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes" (PMID: 20548954). This host-specific adhesion enables the hallmark long-lasting intraerythrocytic bacteremia.

(2) VEGF-driven vasoproliferation via BafA. The Bartonella autotransporter BafA acts as a VEGF analog: "BafA interacts with vascular endothelial growth factor (VEGF) receptor-2 and activates the downstream signaling pathway, suggesting that BafA functions as a VEGF analog. A BafA homolog from a related pathogen, Bartonella quintana, is also functional" (PMID: 32678094). This explains the vasoproliferative lesions (bacillary angiomatosis) directly at the molecular level.

Findings 4 & 10 — Treatment: doxycycline + gentamicin eradicates chronic bacteremia (randomized + meta-analytic evidence)

The best-supported regimen for chronic B. quintana bacteremia is doxycycline plus gentamicin. A randomized open trial (Foucault, Raoult, Brouqui 2003) in homeless patients with blood-culture-positive B. quintana compared gentamicin 3 mg/kg/day IV for 14 days + doxycycline 200 mg/day orally for 28 days versus no treatment. "Intention-to-treat analysis of 20 included patients showed eradication of bacteremia in 7 out of 9 treated patients versus 2 out of 11 untreated controls (P = 0.01). In the per-protocol analysis, eradication was obtained for 7 out of 7 treated patients versus 2 out of 9 untreated controls (P = 0.003)" (PMID: 12821469).

A systematic review and meta-analysis of human bartonellosis treatment corroborates this: "In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate" (PMID: 23602630) — though the authors note the evidence base is limited and dominated by observational studies at high risk of bias. Expert-guideline regimens (Rolain et al. 2004) extend this: endocarditis typically requires prolonged therapy (often doxycycline + an aminoglycoside) and may require valve surgery; bacillary angiomatosis responds to macrolides (erythromycin) or doxycycline given for months. NCIT term suggestions: Doxycycline (NCIT:C692), Gentamicin (NCIT:C575), Erythromycin (NCIT:C608).

Finding 5 — B. quintana has a reduced ~1.58 Mb genome shaped by secondary genome reduction; T4SS drives host adaptation

Comparative genomics of the genus shows Bartonella are α-proteobacteria with host-restricted lifestyles characterized by long-lasting intraerythrocytic infection in a specific mammalian reservoir and arthropod transmission. Among sequenced genomes (circular chromosomes 1.44–2.62 Mb; 1,283–2,136 genes; a synthenic core of 959 genes), B. quintana underwent "massive secondary genome reduction" — it has the smallest genome (~1.58 Mb, ~1,300 genes) — consistent with adaptation to a single human host plus louse vector (PMID: 19696500). The type IV secretion systems (Trw, VirB/VirD4) were laterally acquired and are "type IV secretion systems that adopted prominent roles in host adaptation and specificity" (PMID: 19696500). This reductive evolution reflects the pathogen's dependence on host-derived metabolites (host-integrated metabolism) and its narrow ecological niche.

Finding 6 — Bacillary angiomatosis is epidemiologically linked to homelessness, low income, and lice, with subcutaneous and lytic bone lesions

A case-control study of 49 HIV-associated bacillary angiomatosis-peliosis patients versus 96 matched controls found that 23/49 (47%) were B. quintana and 26/49 (53%) B. henselae. Crucially, tissue tropism differed by species: "Subcutaneous and lytic bone lesions were strongly associated with B. quintana, whereas peliosis hepatis was associated exclusively with B. henselae" (PMID: 9407154). Risk factors also segregated: patients "with B. quintana were clustered and were characterized by low income (P=0.003), homelessness (P = 0.004), and exposure to lice (P= 0.03)", whereas B. henselae was tied to cat/flea exposure (PMID: 9407154). This confirms both the skin/bone tissue tropism of B. quintana and its socioeconomic risk profile.

Finding 7 — Transmission is via infectious body-louse feces (horizontal); no true transovarial (vertical) transmission

Humans acquire B. quintana through contaminated body-louse feces, not the louse bite directly: "Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria" — typically inoculated into skin abrasions or bite-scratch excoriations (PMID: 35803580). Controlled experiments testing vertical transmission found bacterial DNA on egg surfaces (fecal contamination of the egg sheath) but no viable organisms internally: "viable B. quintana could not be cultured from the hemolymph of adult female lice or from within eggs that were surface sterilized, indicating a lack of true transovarial transmission" (PMID: 35803580). Vertical transfer therefore "probably has a limited impact on the dynamics of transmission to humans." This has direct public-health implications: interrupting the human↔louse cycle (delousing) breaks transmission.

Finding 8 — Vomps adhesins and the VirB/D4 T4SS–Bep effector system converge on HIF-1/VEGF to drive vasoproliferation

B. quintana expresses variably expressed outer membrane proteins (Vomps), which are trimeric autotransporter adhesins (TAAs) analogous to B. henselae's Bartonella adhesin A (BadA). In a study of adherence under static and bloodstream-like dynamic flow, investigators "analyzed three different TAAs (Bartonella adhesin A [BadA] of Bartonella henselae, variably expressed outer membrane proteins [Vomps] of Bartonella quintana, and Yersinia adhesin A [YadA] of Yersinia enterocolitica) for mediating bacterial adherence to ECM and endothelial cells" (PMID: 21536788) — establishing Vomps as B. quintana's ECM/endothelial adhesins (binding fibronectin, collagen).

Mechanistically, in the closely related B. henselae the pathway is well defined: "Expression of Bartonella adhesin A (BadA) is crucial for bacterial autoagglutination, adhesion to host cells, binding to extracellular matrix proteins and proangiogenic reprogramming via activation of hypoxia inducible factor (HIF)-1" (PMID: 18627378). In parallel, the VirB/VirD4 T4SS delivers effector proteins into endothelial cells: "VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype" (PMID: 23163798). Notably, BadA and VirB/D4 are frequently mutually exclusive during in vitro passage — a phase-variation phenomenon relevant to culture-dependent diagnostics.

Finding 9 — Humans are the primary reservoir, but B. quintana DNA is increasingly detected in animals; dogs model Bartonella endocarditis

The natural reservoir of B. quintana is humans (NCBI Taxon 9606), transmitted by the body louse. However, molecular surveys increasingly detect B. quintana DNA in non-human hosts. A survey of pet cats in Urmia, Iran found "15 % of the cats (30 out of 200 blood samples) tested positive for the B. quintana gene, with a 95 % confidence interval of 10.71 % to 20.61 %" (100% sequence identity to the reference) (PMID: 38199070). For comparative disease modeling, dogs develop naturally occurring Bartonella endocarditis, making "canids... the most interesting naturally occurring animal model for the human disease" (PMID: 12860639). Experimental mechanistic work uses surrogate rodent-adapted species — "mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum" in adhesion/invasion assays (PMID: 20548954) — and the body louse itself serves as an in-vivo vector model.

Finding 11 — Epidemiology: ~5% of sheltered homeless bacteremic; rising; worldwide wherever body lice occur

In a 4-year study of 930 homeless people in Marseilles, lice were found in 22%, and B. quintana was isolated from blood culture in 50 (5.3%); critically, "the number of bacteremic patient increased from 3.4% to 8.4% (p = 0.02) over the 4 years of the study" — evidence of a rising trend (PMID: 15643300). Geographically, the pathogen is cosmopolitan wherever body-louse infestation occurs: a molecular survey of body lice detected "the presence of B. quintana in lice collected from all locations except the Congo" — spanning France, Russia, Peru, Zimbabwe, and Burundi (PMID: 9986818). B. quintana is one of only three body-louse-borne human pathogens, alongside Rickettsia prowazekii (epidemic typhus) and Borrelia recurrentis (louse-borne relapsing fever); co-exposure occurs, with documented R. prowazekii seroconversion in a B. quintana-bacteremic homeless person (PMID: 15891141).

Mechanistic Model / Interpretation

Ordered causal chain: from louse feces to clinical disease

1.  Body louse (Pediculus humanus humanus) feeds on a bacteremic human
│ leads to
2.  B. quintana replicates in the louse gut and is shed in LOUSE FECES
    (high bacterial concentration; NOT transovarial — no vertical spread)
│ results in
3.  Contaminated feces inoculated into skin abrasions / bite-scratch
    excoriations of a new human host (horizontal transmission)
│ leads to
4.  Bacteria seed a primary niche (endothelial cells / dermal tissue)
│ then (via Trw T4SS)
5.  Trw type IV secretion system mediates HOST-SPECIFIC ADHESION to and
    INVASION of erythrocytes
│ results in
6.  Long-lasting INTRAERYTHROCYTIC BACTEREMIA (immune-privileged niche;
    enables relapsing fever + chronic bacteremia + louse re-acquisition)
│
├─► BRANCH A (acute/chronic systemic disease):
│       relapsing 5-day fever, headache, severe shin/bone pain;
│       chronic afebrile bacteremia → endocarditis (valve
│       vegetations, culture-negative)
│
└─► BRANCH B (vasoproliferative disease, esp. immunocompromised):
Vomps (TAAs) adhere to ECM (fibronectin/collagen) + endothelium
        │ + VirB/D4 T4SS translocates Bep effectors
        │ + BafA autotransporter binds VEGFR-2 (VEGF analog)
        │ results in
HIF-1 activation → VEGF secretion (autocrine/paracrine loop)
inhibition of endothelial apoptosis; invasome-mediated uptake
        │ leads to
ENDOTHELIAL PROLIFERATION → tube formation → ANGIOGENESIS
        │ results in
Bacillary angiomatosis (skin, LYTIC BONE lesions),
vasoproliferative tumors

Upstream vs downstream. The initiating lesion is environmental/behavioral (louse infestation + poverty), not genetic. The most upstream molecular event in host colonization is Trw-mediated erythrocyte tropism, which sustains the bacteremic reservoir. The vasoproliferative arm is downstream of endothelial adhesion (Vomps/BadA) and effector delivery (VirB/D4-Bep, BafA), all converging on the HIF-1 → VEGF hub. Note that Trw (erythrocyte invasion) and VirB/D4 (endothelial reprogramming) are distinct T4SSs with distinct target cells. The HIF-1/VEGF steps are directly demonstrated for B. henselae BadA and inferred for B. quintana via its homologous Vomps and functional BafA homolog.

Cell types and processes (ontology suggestions). - Erythrocyte (CL:0000232) — intracellular niche; GO:0007155 cell adhesion; GO:0044409 entry into host. - Endothelial cell (CL:0000115) — angiogenesis target; GO:0001525 angiogenesis; GO:0043066 negative regulation of apoptotic process; GO:0001666 response to hypoxia (HIF-1). - Anatomical sites (UBERON): blood (UBERON:0000178), skin/dermis (UBERON:0002067), bone (UBERON:0001474), heart valve/endocardium (UBERON:0002165), lymph node (UBERON:0000029), liver (peliosis, mainly B. henselae; UBERON:0002107). - Chemical/biomarker entities (CHEBI): doxycycline (CHEBI:50845); gentamicin (CHEBI:27412).

Comparative species pathophysiology

Feature B. quintana (trench fever) B. henselae (cat-scratch)
Reservoir / vector Human / body louse Cat / cat flea
Adhesin (TAA) Vomps BadA
Risk factors Homelessness, poverty, lice Cat contact, flea exposure
BA tissue tropism Subcutaneous + lytic bone lesions Peliosis hepatis
Genome ~1.58 Mb (most reduced) ~1.9 Mb

Section-by-Section Template Coverage

  • §1 Disease Info / §5 Infectious agent: B. quintana (α-proteobacterium); MONDO:0005991, ICD-10 A79.0, ICD-11 1C30.0, MeSH D014205. Synonyms: five-day/quintan/shin-bone/wolhynia fever, His-Werner disease, urban trench fever. Aggregated disease-level knowledge.
  • §2 Etiology / risk factors: Infectious etiology; risk = homelessness, poverty, low income, body-louse infestation, poor hygiene, cold climate/crowding, alcoholism; immunosuppression (HIV) for vasoproliferative disease. No genetic causal or protective factors (not heritable); no meaningful gene-environment interaction reported.
  • §3 Phenotypes: Fever HP:0001945 (relapsing, ~5-day periodicity), Headache HP:0002315, Bone pain HP:0002653 (shin/tibia), Splenomegaly HP:0001744, Bacteremia HP:0031864, Endocarditis HP:0100584, Lymphadenopathy HP:0002716. Onset acute (adult, occupational/social exposure); severity variable (mild self-limited → severe endocarditis).
  • §4 Genetic/molecular: Not applicable to the human host — no causal genes, pathogenic variants, modifier genes, or chromosomal abnormalities. Relevant "genes" are bacterial virulence loci: trw (T4SS), virB/virD4 (T4SS + bep effectors), vomp family, bafA.
  • §6 Mechanism: See causal chain above.
  • §7 Anatomy: Blood/erythrocytes (primary), vascular endothelium, skin/dermis, bone (lytic lesions), cardiac valves/endocardium, lymph nodes, spleen.
  • §8 Temporal: Incubation ~15–30 days; acute relapsing fever often self-limited over weeks; chronic bacteremia/endocarditis can persist months–years if untreated (chronic, insidious course).
  • §9 Epidemiology: ~5% bacteremia prevalence in sheltered homeless (rising); worldwide wherever body lice occur; predominantly adult; male predominance in homeless cohorts (demographic, not biological). Not inherited — inheritance/penetrance/expressivity sections not applicable.
  • §10 Diagnostics: Serology (IFA IgG, titers ≥1:800 support endocarditis), prolonged blood culture, PCR/sequencing of gltA, ftsZ, 16S rRNA; histopathology (Warthin-Starry silver stain) for bacillary angiomatosis; echocardiography for endocarditis. Differential: culture-negative endocarditis (Coxiella, Tropheryma), other Bartonella, epidemic typhus, relapsing fever.
  • §11 Prognosis: Acute trench fever generally self-limited and non-fatal; endocarditis carries substantial morbidity/mortality and often needs valve surgery; good response to appropriate antibiotics.
  • §12 Treatment: Doxycycline + gentamicin (chronic bacteremia, RCT-supported); doxycycline ± aminoglycoside for endocarditis (+ surgery); macrolides/doxycycline for bacillary angiomatosis.
  • §13 Prevention: Body-louse control (delousing, hygiene, insecticide-treated clothing), improved housing/social conditions, health education; no vaccine (PMID: 20822446).
  • §14 Other species: Human reservoir (NCBI:txid9606); molecular detection in cats/dogs/other animals; dogs = natural endocarditis model.
  • §15 Model organisms: Surrogate rodent-adapted Bartonella (B. birtlesii, B. tribocorum); body louse as vector model; endothelial-cell and erythrocyte in-vitro assays.

Evidence Base

PMID Title (abbrev.) Supports finding(s) Contribution
16494745 B. quintana characteristics and clinical management F1, F2 Causal agent, host/vector restriction, 1915 origin, clinical spectrum, diagnostics
15643300 Ectoparasitism... 930 homeless, Marseilles F1, F11 5.3% bacteremia; rising 3.4%→8.4%; 22% louse prevalence
20548954 Trw T4SS mediates host-specific RBC adhesion F3, F9 Trw T4SS = erythrocyte invasion; surrogate species models
32678094 BafA activates host VEGF pathway F3 BafA = VEGF analog binding VEGFR-2; B. quintana homolog functional
15891120 High prevalence of B. quintana endocarditis, Sfax F2 Endocarditis burden (9.8% of all endocarditis)
23602630 Treatment outcomes of human bartonellosis (meta-analysis) F4 Doxy+gentamicin ↑ resolution of chronic bacteremia
12821469 Randomized trial gentamicin+doxycycline F10 RCT: 7/7 vs 2/9 eradication (P=0.003)
19696500 Genomics of host-restricted Bartonella F5 Massive secondary genome reduction; T4SS host adaptation
9407154 Molecular epidemiology of bacillary angiomatosis F6 Skin/bone tropism; low income/homeless/lice associations
35803580 Vertical transmission in body lice F7 Horizontal fecal transmission; no transovarial spread
21536788 TAA-dependent adherence under flow F8 Vomps = B. quintana TAA; ECM/endothelial adhesion
23163798 BadA interferes with VirB/D4 effector translocation F8 VirB/D4-Bep proangiogenic, anti-apoptotic reprogramming
18627378 BadA head crucial for host cell interaction F8 TAA adhesion → HIF-1 activation
38199070 B. quintana in pet cats, Iran F9 15% cat detection — expanding host range
12860639 Persistent Bartonella bacteremia in humans/animals F9 Dogs as natural endocarditis model
9986818 Body lice as tools for surveillance F11 Worldwide distribution in lice
15891141 Autochthonous epidemic typhus + B. quintana F11 Co-circulation of louse-borne pathogens
20822446 Arthropod-borne diseases & social disorder F4 (prevention) Vector control as primary prevention
11871479 Infections in the homeless F1, F6 Homeless disease context
8727894 B. quintana in seronegative hemodialyzed patient F2 Chronic adenomegaly; seronegative presentation; gentamicin response

Limitations and Knowledge Gaps

  1. Mechanistic inference across species. Much of the vasoproliferative signaling detail (HIF-1 activation, VirB/D4-Bep effector biology, BadA structure–function) is demonstrated in B. henselae and inferred for B. quintana via the homologous Vomps/BafA systems. Direct B. quintana endothelial-reprogramming studies are comparatively sparse. The BafA VEGFR-2 interaction was shown functional for the B. quintana homolog, but the full downstream cascade in B. quintana is extrapolated.

  2. Treatment evidence is thin. The pivotal RCT enrolled only 20 patients (PMID: 12821469), and the meta-analysis explicitly flags that most treatment evidence is observational and at high risk of bias (PMID: 23602630). Optimal duration for endocarditis, and management of relapse, remain guideline/expert-opinion driven.

  3. Epidemiology is likely underestimated. Fastidious culture requirements and non-specific clinical presentation mean cases are under-ascertained; prevalence figures derive largely from urban homeless cohorts in France and may not generalize globally. Population-level incidence rates (new cases/100,000/yr) are not well established.

  4. Expanding host range uncertain in significance. Detection of B. quintana DNA in cats, dogs, non-human primates, and other animals (PMID: 38199070) raises the question of whether animals are competent reservoirs or incidental/spillover hosts. Whether these represent transmission risk to humans is unresolved.

  5. No human genetic component — the template's genetic/variant/inheritance/heritable-model sections are not applicable; any "susceptibility" is socioeconomic and behavioral, not genomic.

  6. Quality-of-life and disability data specific to trench fever (EQ-5D, SF-36, PROMIS) are essentially absent in the literature; QoL impact is inferred from the burden of chronic bacteremia/endocarditis and the comorbidities of the affected homeless population.

Proposed Follow-up Experiments / Actions

  1. Direct B. quintana vasoproliferation assays. Test purified B. quintana BafA and Vomps in human endothelial cells for HIF-1 stabilization, VEGF secretion, tube formation, and apoptosis inhibition — to replace B. henselae inference with species-specific data.

  2. Larger, multicenter treatment trial. A pragmatic RCT (or well-designed prospective registry) across multiple homeless-service settings to define the optimal antibiotic regimen and duration for chronic bacteremia and endocarditis, and to quantify relapse.

  3. Global surveillance via body lice. Extend the molecular-surveillance approach (PMID: 9986818) to systematically map B. quintana prevalence in body lice and homeless populations worldwide, including incidence estimation.

  4. Reservoir-competence studies in animals. Determine whether cats/dogs/primates with detectable B. quintana DNA harbor viable, transmissible bacteria and whether alternative arthropod vectors participate — clarifying zoonotic risk.

  5. Public-health intervention evaluation. Rigorously evaluate delousing/hygiene/housing interventions for their effect on B. quintana incidence, integrating vector control per PMID: 20822446.

  6. Biomarker/diagnostic development. Develop rapid point-of-care serologic or molecular assays suited to low-resource, homeless-service settings to improve case ascertainment and shorten time-to-treatment.

Consensus Answer

Trench fever is a louse-borne bacterial infection caused by Bartonella quintana (MONDO:0005991; ICD-10 A79.0), a human-restricted α-proteobacterium transmitted through the feces of the body louse (Pediculus humanus humanus) and re-emerging among the urban homeless worldwide. It is not a genetic disease — risk is socioeconomic (homelessness, poverty, body lice, poor hygiene; immunosuppression for vasoproliferative forms) — and it spans a clinical spectrum from classic relapsing five-day fever with shin pain to chronic bacteremia, culture-negative endocarditis, and bacillary angiomatosis, driven mechanistically by Trw-T4SS–mediated erythrocyte invasion plus Vomps/BadA-, VirB/D4-Bep–, and BafA-driven HIF-1/VEGF endothelial proliferation. It is effectively treated with doxycycline plus gentamicin (randomized-trial evidence) and prevented by body-louse control; no vaccine exists.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome Count
References checked 20
Resolved 20
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 20
On topic 15
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 26
Resolved 26
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0
Terms whose name was checked 5
Terms named correctly 2
Terms named as a different term 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:0005991 (5 mentions) - the report calls it "if available"; MONDO calls it trench fever
  • HP:0001945 (2 mentions) - the report calls it "relapsing, ~5-day periodicity"; HP calls it Fever
  • HP:0002653 (2 mentions) - the report calls it "shin/tibia"; HP calls it Bone pain