⚙

Pathophysiology

5

Inhalation and Intracellular Replication in Alveolar Macrophages

Q fever follows inhalation of aerosolized Coxiella burnetii, which is an obligate intracellular bacterium that replicates within alveolar macrophages in a lysosome-derived replicative vacuole. This intracellular lifestyle is the basis for the requirement for cell-penetrant antibiotics, because beta-lactams cannot reach the cytoplasmic organism.

alveolar macrophage CL:0000583

symbiont entry into host cell GO:0046718 biological process involved in interaction with host GO:0051701

Downstream

Acute Q Fever (Pneumonia and Hepatitis) Intracellular replication produces the acute febrile, pneumonic, and hepatic syndromes.

Coxiella Ribosomal Translation (Tetracycline Target) The organism's ribosome is the molecular target of tetracycline therapy.

Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion After uptake, the organism establishes the replication-permissive Coxiella-containing vacuole using Dot/Icm-secreted effectors.

Show evidence (2 references)

PMID:42075771 SUPPORT Other

"C. burnetii (Cb) is an obligate intracellular bacterial pathogen that replicates within alveolar macrophages following aerosol infection."

Establishes Coxiella burnetii as an obligate intracellular pathogen replicating in alveolar macrophages after aerosol infection. Evidence source is OTHER as this is a review article.

PMID:12762362 SUPPORT Other

"This spore-forming microorganism is a small gram-negative coccobacillus that is an obligate intracellular parasite."

Confirms C. burnetii as an obligate intracellular parasite, the basis for the intracellular-niche conformance. Evidence source is OTHER as this is a review article.

Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion

Intracellular replication of C. burnetii depends on maturation of a phagolysosome-like, acidic replication-permissive Coxiella-containing vacuole (CCV). Effectors delivered by the Dot/Icm type IV secretion system are indispensable for building and maintaining a single large CCV (e.g., CvpE, which perturbs lysosomal PIKfyve/TRPML1 activity to block vacuole fission and autolysosomal clearance), allowing the organism to evade host cell clearance. The acidic CCV also underlies the pharmacology of chronic-Q-fever therapy: alkalinizing the compartment with hydroxychloroquine restores the bactericidal activity of doxycycline.

alveolar macrophage CL:0000583

Downstream

Acute Q Fever (Pneumonia and Hepatitis) Successful CCV biogenesis and intracellular replication drive the acute clinical syndromes.

Chronic Q Fever (Persistent Focalized Infection and Endocarditis) Persistence within the CCV underlies focalized chronic infection.

Show evidence (2 references)

PMID:38725096 SUPPORT In Vitro

"Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV)."

Establishes the phagolysosome-like Coxiella-containing vacuole as the required intracellular replicative niche. Evidence source is IN_VITRO (cell-based effector study).

PMID:38725096 SUPPORT In Vitro

"Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles."

Documents the Dot/Icm type IV secretion system effectors as indispensable for Coxiella-containing vacuole biogenesis. Evidence source is IN_VITRO.

Chronic Q Fever (Persistent Focalized Infection and Endocarditis)

In a minority of infections, C. burnetii persists as a focalized infection that manifests months to years later, most characteristically as culture-negative endocarditis (and vascular infection). Under the current paradigm, persistent infection requires a pre-existing focus (e.g., damaged or prosthetic heart valve, vascular aneurysm/graft); it requires prolonged combination antimicrobial therapy.

inflammatory response GO:0006954 ↑ INCREASED

heart UBERON:0000948

Show evidence (2 references)

PMID:37679410 SUPPORT Other

"Q fever manifests as an acute self-limiting febrile illness or as a chronic disease with complications such as vasculitis and endocarditis."

Documents the chronic arm of Q fever with vasculitis and endocarditis as complications. Evidence source is OTHER (review article).

PMID:27856520 SUPPORT Other

"no persistent infection can exist without a focus of infection"

Supports the paradigm that chronic/persistent C. burnetii infection requires a pre-existing focus. Evidence source is OTHER (review article).

Acute Q Fever (Pneumonia and Hepatitis)

Acute Q fever manifests as one of three syndromes: a nonspecific febrile illness, pneumonia (which can range from mild to severe requiring ventilation, classically with multiple round opacities on chest radiography), or hepatitis.

inflammatory response GO:0006954 ↑ INCREASED

lung UBERON:0002048

Show evidence (1 reference)

PMID:12762362 SUPPORT Other

"There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis."

Documents the three acute Q fever syndromes (febrile illness, pneumonia, hepatitis). Evidence source is OTHER as this is a review article.

Coxiella Ribosomal Translation (Tetracycline Target)

C. burnetii depends on its bacterial ribosome for protein synthesis. Doxycycline, a tetracycline, binds the 30S ribosomal subunit and arrests bacterial protein synthesis; this ribosomal target — combined with doxycycline's intracellular penetration — is why a tetracycline rather than a beta-lactam is first-line.

translation GO:0006412

Show evidence (1 reference)

PMID:24336183 SUPPORT Other

"The ribosome is one of the main antibiotic targets in the bacterial cell."

Establishes the bacterial ribosome as the target of tetracyclines and other protein-synthesis inhibitors, the step this node represents. Evidence source is OTHER as this is a review article.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

5

Digestive 1

Hepatitis HP:0012115

Show evidence (1 reference)

PMID:12762362 SUPPORT Other

"There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis."

Hepatitis is one of the three acute Q fever syndromes. Evidence source is OTHER as this is a review article.

Immune 1

Pneumonia HP:0002090

Show evidence (1 reference)

PMID:12762362 SUPPORT Other

"There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis."

Pneumonia is one of the three acute Q fever syndromes. Evidence source is OTHER as this is a review article.

Metabolism 1

Fever HP:0001945

Show evidence (1 reference)

PMID:12762362 SUPPORT Other

"There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis."

Nonspecific febrile illness is one of the three acute Q fever syndromes. Evidence source is OTHER as this is a review article.

Other 2

Q Fever Endocarditis Bacterial endocarditis HP:0006689

Temporal: CHRONIC

Show evidence (2 references)

PMID:37679410 SUPPORT Other

"Q fever manifests as an acute self-limiting febrile illness or as a chronic disease with complications such as vasculitis and endocarditis."

Identifies endocarditis as a complication of chronic Q fever. Evidence source is OTHER (review article).

PMID:9927100 SUPPORT Human Clinical

"Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to 60% of patients."

Quantifies the high case fatality of untreated Q fever endocarditis in a clinical cohort.

Q Fever Fatigue Syndrome OCCASIONAL Chronic fatigue HP:0012432

Show evidence (1 reference)

PMID:28329131 SUPPORT Human Clinical

"Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS)."

Establishes Q fever fatigue syndrome in ~20% of acute Q fever patients, supporting both the phenotype and the OCCASIONAL frequency band (5-29%).

💊

Medical Actions

3

Doxycycline

Action: Pharmacotherapy NCIT:C15986

Agent: doxycycline CHEBI:50845

Tetracycline antibiotic that accumulates intracellularly and inhibits bacterial protein synthesis at the 30S ribosome; the preferred treatment for Q fever because it reaches the intracellular organism. A fluoroquinolone is an alternative; macrolide susceptibility is variable.

Mechanism Target:

INHIBITS Coxiella Ribosomal Translation (Tetracycline Target) — Doxycycline binds the 30S ribosome and arrests C. burnetii protein synthesis, the molecular target that makes a tetracycline first-line.

INHIBITS Inhalation and Intracellular Replication in Alveolar Macrophages — Doxycycline accumulates intracellularly and so reaches the cytoplasmic organism that beta-lactams cannot.

Show evidence (1 reference)

PMID:12762362 SUPPORT Other

"Treatment with doxycycline or a fluoroquinolone is preferred."

Identifies doxycycline (or a fluoroquinolone) as the preferred treatment for Q fever. Evidence source is OTHER as this is a review article.

Doxycycline plus Hydroxychloroquine

Action: Pharmacotherapy NCIT:C15986

Agent: doxycycline CHEBI:50845 hydroxychloroquine CHEBI:5801

Combination regimen for chronic Q fever / Q fever endocarditis. Doxycycline inhibits the bacterial ribosome, and hydroxychloroquine alkalinizes the acidic Coxiella-containing vacuole, restoring the bactericidal activity of doxycycline against the intracellular organism. Given for at least 18 months, it shortens therapy duration and reduces relapse compared with the older doxycycline-plus-quinolone regimen.

Mechanism Target:

INHIBITS Coxiella Ribosomal Translation (Tetracycline Target) — Doxycycline arrests bacterial protein synthesis; hydroxychloroquine alkalinizes the CCV so doxycycline becomes bactericidal.

INHIBITS Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion — Hydroxychloroquine raises the pH of the acidic Coxiella-containing vacuole, the intracellular niche in which the organism persists.

Show evidence (1 reference)

PMID:9927100 SUPPORT Human Clinical

"Prescription of the doxycycline and hydroxychloroquine combination for at least 18 months allows shortening of the duration of therapy and reduction in the number of relapses."

Clinical trial evidence that doxycycline plus hydroxychloroquine for ≥18 months shortens therapy and reduces relapse in Q fever endocarditis.

Q Fever Vaccination (Q-VAX)

Action: vaccination Ontology label: Vaccination NCIT:C15346

Q-VAX is a formalin-inactivated whole-cell phase I C. burnetii vaccine used for pre-exposure prophylaxis in at-risk occupational groups (e.g., abattoir workers) in Australia. Worldwide use is limited by reactogenic reactions in individuals already sensitized to the organism, requiring pre-vaccination screening.

Show evidence (1 reference)

PMID:37679410 SUPPORT Other

"The current preventative human Q fever vaccine Q-VAX poses limitations on its worldwide implementation due to reactogenic responses in pre-sensitized individuals."

Documents Q-VAX as the current human Q fever vaccine and its reactogenicity limitation. Evidence source is OTHER (review article).

📊

Related Datasets

3

A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever geo:GSE112086

Coxiella burnetii, the agent causing Q fever, has been associated with B-cell non-Hodgkin lymphoma (NHL). To better clarify this link, we analysed the genetic transcriptomic profile of peripheral blood leukocytes from patients with C. burnetii infection to identify possible links to lymphoma. Microarray analyses revealed that 1189 genes were expressed differently (p <.001 and fold change ≥4) in whole blood of patients with C. burnetii infection compared to controls. In addition, 95 genes expressed in patients with non-Hodgkin lymphoma (NHL) and in patients with C. burnetii persistent infection have allowed us to establish the ‘C. burnetii-associated NHL signature’.

human MICROARRAY n=21

PMID:31181104

Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.

Granulomatous response to Coxiella burnetii, the agent of Q fever: Activation of type I interferon-related genes geo:GSE37666

The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells compared with peripheral blood mononuclear cells. About 60% of modulated genes were common to C. burnetii and BCG granulomas including M1-related genes. C.

human MICROARRAY n=12

PMID:25566510

Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.

Interferon-γ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever geo:GSE66476

Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-γ response in chronic Q fever patients. Methods: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-γ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals. Results: IFN-γ production by PBMCs of chronic Q fever patients incubated with C.

human MICROARRAY n=30

Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.

{ }

Source YAML

click to show

name: Q Fever
creation_date: "2026-06-28T00:00:00Z"
description: >
Q fever is a zoonotic infection caused by Coxiella burnetii, an obligate
intracellular Gram-negative bacterium that replicates within alveolar macrophages
after inhalation of contaminated aerosols (the reservoir is livestock, with high
organism concentrations in the placenta of infected animals). Acute Q fever
presents as one of three syndromes — nonspecific febrile illness, pneumonia, or
hepatitis — while chronic Q fever is most often endocarditis. Because the
organism is intracellular, treatment requires cell-penetrant antibiotics;
doxycycline (a tetracycline acting on the bacterial ribosome) or a fluoroquinolone
is preferred, and beta-lactams are ineffective.
category: Infectious Disease
parents:
- Bacterial Respiratory Infection
synonyms:
- Coxiella burnetii infection
- Coxiellosis
disease_term:
preferred_term: Q fever
term:
id: MONDO:0019186
label: Q fever
pathophysiology:
- name: Inhalation and Intracellular Replication in Alveolar Macrophages
role: trigger
conforms_to: "intracellular_pathogen_persistence#Intracellular Niche and Beta-Lactam Exclusion"
description: >
Q fever follows inhalation of aerosolized Coxiella burnetii, which is an
obligate intracellular bacterium that replicates within alveolar macrophages in
a lysosome-derived replicative vacuole. This intracellular lifestyle is the
basis for the requirement for cell-penetrant antibiotics, because beta-lactams
cannot reach the cytoplasmic organism.
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: symbiont entry into host cell
term:
id: GO:0046718
label: symbiont entry into host cell
- preferred_term: biological process involved in interaction with host
term:
id: GO:0051701
label: biological process involved in interaction with host
evidence:
- reference: PMID:42075771
reference_title: "Subverting Host Defense from Within: Innate Immune Modulation by Coxiella burnetii."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
C. burnetii (Cb) is an obligate intracellular bacterial pathogen that
replicates within alveolar macrophages following aerosol infection.
explanation: >-
Establishes Coxiella burnetii as an obligate intracellular pathogen
replicating in alveolar macrophages after aerosol infection. Evidence source
is OTHER as this is a review article.
- reference: PMID:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
This spore-forming microorganism is a small gram-negative coccobacillus that
is an obligate intracellular parasite.
explanation: >-
Confirms C. burnetii as an obligate intracellular parasite, the basis for the
intracellular-niche conformance. Evidence source is OTHER as this is a review
article.
downstream:
- target: Acute Q Fever (Pneumonia and Hepatitis)
description: >-
Intracellular replication produces the acute febrile, pneumonic, and hepatic
syndromes.
- target: Coxiella Ribosomal Translation (Tetracycline Target)
description: >-
The organism's ribosome is the molecular target of tetracycline therapy.
- target: Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion
description: >-
After uptake, the organism establishes the replication-permissive
Coxiella-containing vacuole using Dot/Icm-secreted effectors.

- name: Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion
role: mechanism
conforms_to: "intracellular_pathogen_persistence#Intracellular Niche and Beta-Lactam Exclusion"
description: >
Intracellular replication of C. burnetii depends on maturation of a
phagolysosome-like, acidic replication-permissive Coxiella-containing vacuole
(CCV). Effectors delivered by the Dot/Icm type IV secretion system are
indispensable for building and maintaining a single large CCV (e.g., CvpE,
which perturbs lysosomal PIKfyve/TRPML1 activity to block vacuole fission and
autolysosomal clearance), allowing the organism to evade host cell clearance.
The acidic CCV also underlies the pharmacology of chronic-Q-fever therapy:
alkalinizing the compartment with hydroxychloroquine restores the
bactericidal activity of doxycycline.
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
evidence:
- reference: PMID:38725096
reference_title: "Coxiella burnetii effector CvpE maintains biogenesis of Coxiella-containing vacuoles by suppressing lysosome tubulation through binding PI(3)P and perturbing PIKfyve activity on lysosomes."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Intracellular replication of C. burnetii requires the maturation of a
phagolysosome-like compartment known as the replication permissive
Coxiella-containing vacuole (CCV).
explanation: >-
Establishes the phagolysosome-like Coxiella-containing vacuole as the
required intracellular replicative niche. Evidence source is IN_VITRO
(cell-based effector study).
- reference: PMID:38725096
reference_title: "Coxiella burnetii effector CvpE maintains biogenesis of Coxiella-containing vacuoles by suppressing lysosome tubulation through binding PI(3)P and perturbing PIKfyve activity on lysosomes."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Effector proteins secreted by the Dot/Icm secretion system are
indispensable for maturation of a single large CCV by facilitating the
fusion of promiscuous vesicles.
explanation: >-
Documents the Dot/Icm type IV secretion system effectors as indispensable
for Coxiella-containing vacuole biogenesis. Evidence source is IN_VITRO.
downstream:
- target: Acute Q Fever (Pneumonia and Hepatitis)
description: >-
Successful CCV biogenesis and intracellular replication drive the acute
clinical syndromes.
- target: Chronic Q Fever (Persistent Focalized Infection and Endocarditis)
description: >-
Persistence within the CCV underlies focalized chronic infection.

- name: Chronic Q Fever (Persistent Focalized Infection and Endocarditis)
role: consequence
description: >
In a minority of infections, C. burnetii persists as a focalized infection
that manifests months to years later, most characteristically as
culture-negative endocarditis (and vascular infection). Under the current
paradigm, persistent infection requires a pre-existing focus (e.g., damaged
or prosthetic heart valve, vascular aneurysm/graft); it requires prolonged
combination antimicrobial therapy.
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
locations:
- preferred_term: heart
term:
id: UBERON:0000948
label: heart
evidence:
- reference: PMID:37679410
reference_title: "Q fever immunology: the quest for a safe and effective vaccine."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Q fever manifests as an acute self-limiting febrile illness or as a chronic
disease with complications such as vasculitis and endocarditis.
explanation: >-
Documents the chronic arm of Q fever with vasculitis and endocarditis as
complications. Evidence source is OTHER (review article).
- reference: PMID:27856520
reference_title: "From Q Fever to Coxiella burnetii Infection: a Paradigm Change."
supports: SUPPORT
evidence_source: OTHER
snippet: "no persistent infection can exist without a focus of infection"
explanation: >-
Supports the paradigm that chronic/persistent C. burnetii infection
requires a pre-existing focus. Evidence source is OTHER (review article).
downstream: []

- name: Acute Q Fever (Pneumonia and Hepatitis)
role: consequence
description: >
Acute Q fever manifests as one of three syndromes: a nonspecific febrile
illness, pneumonia (which can range from mild to severe requiring ventilation,
classically with multiple round opacities on chest radiography), or hepatitis.
biological_processes:
- 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:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
There are three distinct clinical syndromes of the acute form of the illness:
nonspecific febrile illness, pneumonia, and hepatitis.
explanation: >-
Documents the three acute Q fever syndromes (febrile illness, pneumonia,
hepatitis). Evidence source is OTHER as this is a review article.
downstream: []

- name: Coxiella Ribosomal Translation (Tetracycline Target)
role: therapeutic_vulnerability
conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
description: >
C. burnetii depends on its bacterial ribosome for protein synthesis. Doxycycline,
a tetracycline, binds the 30S ribosomal subunit and arrests bacterial protein
synthesis; this ribosomal target — combined with doxycycline's intracellular
penetration — is why a tetracycline rather than a beta-lactam is first-line.
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: >-
Establishes the bacterial ribosome as the target of tetracyclines and other
protein-synthesis inhibitors, the step this node represents. Evidence source
is OTHER as this is a review article.
downstream: []
phenotypes:
- category: Respiratory
name: Pneumonia
description: >
Pneumonia is one of the three acute Q fever syndromes, ranging from mild to
severe.
phenotype_term:
preferred_term: Pneumonia
term:
id: HP:0002090
label: Pneumonia
evidence:
- reference: PMID:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
There are three distinct clinical syndromes of the acute form of the illness:
nonspecific febrile illness, pneumonia, and hepatitis.
explanation: >-
Pneumonia is one of the three acute Q fever syndromes. Evidence source is
OTHER as this is a review article.
- category: Constitutional
name: Fever
description: >
A nonspecific febrile illness is one of the acute Q fever presentations.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
evidence:
- reference: PMID:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
There are three distinct clinical syndromes of the acute form of the illness:
nonspecific febrile illness, pneumonia, and hepatitis.
explanation: >-
Nonspecific febrile illness is one of the three acute Q fever syndromes.
Evidence source is OTHER as this is a review article.
- category: Hepatic
name: Hepatitis
description: >
Hepatitis is one of the three acute Q fever syndromes.
phenotype_term:
preferred_term: Hepatitis
term:
id: HP:0012115
label: Hepatitis
evidence:
- reference: PMID:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
There are three distinct clinical syndromes of the acute form of the illness:
nonspecific febrile illness, pneumonia, and hepatitis.
explanation: >-
Hepatitis is one of the three acute Q fever syndromes. Evidence source is
OTHER as this is a review article.
- category: Cardiovascular
name: Q Fever Endocarditis
description: >
Culture-negative endocarditis is the most common manifestation of chronic
Q fever, typically arising on a pre-existing valvular lesion, and carries
high untreated mortality.
phenotype_term:
preferred_term: Q fever (Coxiella) endocarditis
term:
id: HP:0006689
label: Bacterial endocarditis
temporality: CHRONIC
evidence:
- reference: PMID:37679410
reference_title: "Q fever immunology: the quest for a safe and effective vaccine."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Q fever manifests as an acute self-limiting febrile illness or as a chronic
disease with complications such as vasculitis and endocarditis.
explanation: >-
Identifies endocarditis as a complication of chronic Q fever. Evidence
source is OTHER (review article).
- reference: PMID:9927100
reference_title: "Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to 60%
of patients.
explanation: >-
Quantifies the high case fatality of untreated Q fever endocarditis in a
clinical cohort.
- category: Constitutional
name: Q Fever Fatigue Syndrome
description: >
A post-infectious chronic fatigue syndrome develops in roughly one-fifth of
patients after acute Q fever, producing prolonged fatigue and functional
impairment.
phenotype_term:
preferred_term: Q fever fatigue syndrome
term:
id: HP:0012432
label: Chronic fatigue
frequency: OCCASIONAL
evidence:
- reference: PMID:28329131
reference_title: "Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Approximately 20% of patients with acute Q fever will develop chronic
fatigue, referred to as Q fever fatigue syndrome (QFS).
explanation: >-
Establishes Q fever fatigue syndrome in ~20% of acute Q fever patients,
supporting both the phenotype and the OCCASIONAL frequency band (5-29%).
treatments:
- name: Doxycycline
description: >
Tetracycline antibiotic that accumulates intracellularly and inhibits bacterial
protein synthesis at the 30S ribosome; the preferred treatment for Q fever
because it reaches the intracellular organism. A fluoroquinolone is an
alternative; macrolide susceptibility is variable.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: doxycycline
term:
id: CHEBI:50845
label: doxycycline
target_mechanisms:
- target: Coxiella Ribosomal Translation (Tetracycline Target)
treatment_effect: INHIBITS
description: >-
Doxycycline binds the 30S ribosome and arrests C. burnetii protein synthesis,
the molecular target that makes a tetracycline first-line.
- target: Inhalation and Intracellular Replication in Alveolar Macrophages
treatment_effect: INHIBITS
description: >-
Doxycycline accumulates intracellularly and so reaches the cytoplasmic
organism that beta-lactams cannot.
evidence:
- reference: PMID:12762362
reference_title: Coxiella burnetii pneumonia.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Treatment with doxycycline or a fluoroquinolone is preferred.
explanation: >-
Identifies doxycycline (or a fluoroquinolone) as the preferred treatment for
Q fever. Evidence source is OTHER as this is a review article.
- name: Doxycycline plus Hydroxychloroquine
description: >
Combination regimen for chronic Q fever / Q fever endocarditis. Doxycycline
inhibits the bacterial ribosome, and hydroxychloroquine alkalinizes the acidic
Coxiella-containing vacuole, restoring the bactericidal activity of doxycycline
against the intracellular organism. Given for at least 18 months, it shortens
therapy duration and reduces relapse compared with the older
doxycycline-plus-quinolone regimen.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: doxycycline
term:
id: CHEBI:50845
label: doxycycline
- preferred_term: hydroxychloroquine
term:
id: CHEBI:5801
label: hydroxychloroquine
target_mechanisms:
- target: Coxiella Ribosomal Translation (Tetracycline Target)
treatment_effect: INHIBITS
description: >-
Doxycycline arrests bacterial protein synthesis; hydroxychloroquine
alkalinizes the CCV so doxycycline becomes bactericidal.
- target: Coxiella-Containing Vacuole Biogenesis and Dot/Icm Effector Secretion
treatment_effect: INHIBITS
description: >-
Hydroxychloroquine raises the pH of the acidic Coxiella-containing vacuole,
the intracellular niche in which the organism persists.
evidence:
- reference: PMID:9927100
reference_title: "Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Prescription of the doxycycline and hydroxychloroquine combination for at
least 18 months allows shortening of the duration of therapy and reduction
in the number of relapses.
explanation: >-
Clinical trial evidence that doxycycline plus hydroxychloroquine for ≥18
months shortens therapy and reduces relapse in Q fever endocarditis.
- name: Q Fever Vaccination (Q-VAX)
description: >
Q-VAX is a formalin-inactivated whole-cell phase I C. burnetii vaccine used
for pre-exposure prophylaxis in at-risk occupational groups (e.g., abattoir
workers) in Australia. Worldwide use is limited by reactogenic reactions in
individuals already sensitized to the organism, requiring pre-vaccination
screening.
therapeutic_modality: VACCINE
treatment_term:
preferred_term: vaccination
term:
id: NCIT:C15346
label: Vaccination
evidence:
- reference: PMID:37679410
reference_title: "Q fever immunology: the quest for a safe and effective vaccine."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The current preventative human Q fever vaccine Q-VAX poses limitations on
its worldwide implementation due to reactogenic responses in pre-sensitized
individuals.
explanation: >-
Documents Q-VAX as the current human Q fever vaccine and its reactogenicity
limitation. Evidence source is OTHER (review article).
notes: >
Created as part of the Respiratory Infections project. Intracellular zoonotic
atypical pneumonia; conforms to the intracellular_pathogen_persistence module
(intracellular niche / cell-penetrant-drug requirement) and the
bacterial_protein_synthesis_inhibition module (tetracycline ribosomal target),
mirroring the Murine_Typhus doxycycline pattern. Chronic Q fever is now modeled:
a Coxiella-containing-vacuole/Dot-Icm effector node, a chronic-infection/
endocarditis pathophysiology node, Q fever endocarditis and Q fever fatigue
syndrome phenotypes, and the doxycycline+hydroxychloroquine combination and
Q-VAX vaccination treatments. The infectious_agent (NCBITaxon) block was omitted
at creation and Coxiella burnetii is described in the text.
datasets:
- accession: geo:GSE112086
title: A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever
description: Coxiella burnetii, the agent causing Q fever, has been associated with B-cell non-Hodgkin lymphoma (NHL). To better clarify this link, we analysed the genetic transcriptomic profile of peripheral blood leukocytes from patients with C. burnetii infection to identify possible links to lymphoma. Microarray analyses revealed that 1189 genes were expressed differently (p <.001 and fold change ≥4) in whole blood of patients with C. burnetii infection compared to controls. In addition, 95 genes expressed in patients with non-Hodgkin lymphoma (NHL) and in patients with C. burnetii persistent infection have allowed us to establish the ‘C. burnetii-associated NHL signature’.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_count: 21
publication: PMID:31181104
notes: Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE37666
title: 'Granulomatous response to Coxiella burnetii, the agent of Q fever: Activation of type I interferon-related genes '
description: The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells compared with peripheral blood mononuclear cells. About 60% of modulated genes were common to C. burnetii and BCG granulomas including M1-related genes. C.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_count: 12
publication: PMID:25566510
notes: Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE66476
title: Interferon-γ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever
description: 'Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-γ response in chronic Q fever patients. Methods: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-γ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals. Results: IFN-γ production by PBMCs of chronic Q fever patients incubated with C.'
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_count: 30
notes: Identified by GEO DataSets index search for Q Fever (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.

📚

References & Deep Research

Deep Research

1

Falcon ▸

References

Edison Scientific Literature 33 citations 2026-07-05T19:06:59.109777

1. Disease Information

Q fever is a globally distributed zoonotic disease caused by the Gram-negative, obligate intracellular bacterium Coxiella burnetii. It primarily affects animals (notably ruminants) but can infect humans, resulting in variable clinical manifestations ranging from asymptomatic infection to severe acute and chronic disease.

Category	Identifier/Value
Disease Name	Q fever (OpenTargets Search: Q Fever, fatima2025epidemiologyaetiologymode pages 3-5)
MONDO ID	MONDO:0019186 (OpenTargets Search: Q Fever)
ICD-10	A78
ICD-11	1C33
MeSH	D011778
Causative Agent	Coxiella burnetii (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2)
Classification	Gram-negative obligate intracellular bacterium; family Coxiellaceae; order Legionellales (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2)
Synonyms	Query fever; Coxiellosis (fatima2025epidemiologyaetiologymode pages 1-3, fatima2025epidemiologyaetiologymode pages 5-7)
Category	Zoonotic infectious disease (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2)
BSL Level	BSL-3
CDC Category	Category B bioterrorism agent
Geographic Distribution	Worldwide except New Zealand (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2)

Table: This table summarizes core disease identifiers and defining characteristics for Q fever, including ontology mapping, microbiologic classification, and epidemiologic scope. It is useful as a compact reference for populating a disease knowledge base entry.

Synonyms

Query fever
Coxiellosis

Key Identifiers

MONDO ID: MONDO:0019186
ICD-10: A78
ICD-11: 1C33
MeSH: D011778
BSL-3 Pathogen
CDC Category B bioterrorism agent

Data is primarily aggregated from disease-level resources, epidemiological surveillance, and systematic reviews (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2).

2. Etiology

Primary causal factor: Infection by Coxiella burnetii. The principal transmission to humans is via inhalation of infected aerosols from the birth fluids, excreta, or wool of infected ruminants (fatima2025epidemiologyaetiologymode pages 3-5, christodoulou2023anarrativereview pages 1-2).

Risk Factors: - Occupational exposure (farmers, veterinarians, abattoir/laboratory workers) - Proximity to livestock (especially sheep, cattle, goats) - Immunocompromised state - Consumption of unpasteurized dairy products

Environmental: The bacterium is highly resilient, capable of environmental survival and airborne spread, leading to windborne outbreaks (fatima2025epidemiologyaetiologymode pages 3-5, fatima2025epidemiologyaetiologymode pages 5-7).

Genetic factors: No established direct genetic risk factors in host; virulence differences are linked to bacterial plasmid content and LPS phase variation (fatima2025epidemiologyaetiologymode pages 7-9).

Protective Factors: - Vaccination (Q-VAX) in endemic regions or at-risk populations (fatima2025epidemiologyaetiologymode pages 18-20, sam2023qfeverimmunology pages 5-6)

3. Phenotypes

Key clinical phenotypes are succinctly summarized below.

Phenotype	Type	Frequency	Severity	HPO Term
Fever (fatima2025epidemiologyaetiologymode pages 9-11)	Symptom	~40% of infected	Variable	HP:0001945
Fatigue (fatima2025epidemiologyaetiologymode pages 9-11)	Symptom	Common	Moderate-severe	HP:0012378
Headache (fatima2025epidemiologyaetiologymode pages 9-11)	Symptom	Common	Moderate	HP:0002315
Myalgia (fatima2025epidemiologyaetiologymode pages 9-11)	Symptom	Common	Mild-moderate	HP:0003326
Pneumonia (fatima2025epidemiologyaetiologymode pages 9-11)	Complication	Variable	Severe	HP:0002090
Hepatitis (fatima2025epidemiologyaetiologymode pages 9-11)	Complication	Variable	Moderate-severe	HP:0012115
Endocarditis (fatima2025epidemiologyaetiologymode pages 9-11, fatima2025epidemiologyaetiologymode pages 16-18)	Chronic complication	~5% of infected	Severe/life-threatening	HP:0001695
Q fever fatigue syndrome (NCT01318356 chunk 2)	Sequela	~20% post-acute	Moderate-severe	HP:0012432
Encephalitis (fatima2025epidemiologyaetiologymode pages 9-11)	Rare complication	Rare	Severe	HP:0002383
Meningitis (fatima2025epidemiologyaetiologymode pages 9-11)	Rare complication	Rare	Severe	HP:0001287

Table: This table summarizes major Q fever clinical phenotypes and complications, with approximate frequency, severity, and suggested HPO mappings. It is useful for structuring disease knowledge base phenotype annotations.

Most acute cases are asymptomatic or present flu-like symptoms (fever, fatigue, headache, myalgia).
Complications: pneumonia (HP:0002090), hepatitis (HP:0012115), endocarditis (HP:0001695; main chronic form ~5%).
Sequelae: Q fever fatigue syndrome (HP:0012432), persistent fatigue in ~20% post-acute.
Severe complications include encephalitis and meningitis (rare).

Age of onset: All ages, with increased risk of chronic sequelae in older/immunosuppressed patients (fatima2025epidemiologyaetiologymode pages 9-11).

4. Genetic/Molecular Information

Q fever is not classically genetic; it is a direct result of infection with C. burnetii. Important molecular/strain features include: - Phase I LPS (smooth, full-length) = virulent; Phase II LPS (rough, truncated) = avirulent (fatima2025epidemiologyaetiologymode pages 5-7, fatima2025epidemiologyaetiologymode pages 7-9). - Plasmid types (QpH1, QpRS) and strain-specific virulence; Groups I–III linked to acute disease, Group IV to chronic forms (fatima2025epidemiologyaetiologymode pages 7-9). - Dot/Icm Type IV Secretion System (T4BSS) delivers effectors (notably CvpE), central to intracellular survival and virulence (sam2023qfeverimmunology pages 2-2, fatima2025epidemiologyaetiologymode pages 5-7, zhao2024coxiellaburnetiieffector pages 1-2).

5. Environmental Information

Key factors: - Persistence in environment (dust, animal sheds), airborne dispersal potential (fatima2025epidemiologyaetiologymode pages 3-5). - Primary human exposure: inhalation of aerosols in occupational/animal contact settings, ingestion of unpasteurized dairy (fatima2025epidemiologyaetiologymode pages 3-5). - Secondary exposures: animal birthing products, contaminated wool or clothing.

6. Mechanism / Pathophysiology

Entry/Survival: C. burnetii survives and replicates within the Coxiella-containing vacuole (CCV) in host cells, primarily alveolar macrophages (sam2023qfeverimmunology pages 2-2, sam2023qfeverimmunology pages 1-2).
Effector Functions: The Dot/Icm T4BSS delivers effectors (e.g., CvpE) that modify host endolysosomal compartments, inhibit host autophagy/apoptosis, and delay phagolysosomal maturation (sam2023qfeverimmunology pages 2-2, zhao2024coxiellaburnetiieffector pages 1-2, zhao2024coxiellaburnetiieffector pages 5-7).
Phase variation: Phase I LPS impedes complement and immune recognition; phase II is less virulent and more susceptible to immune clearance (fatima2025epidemiologyaetiologymode pages 5-7).
Immune Evasion: Inhibits apoptosis, alters macrophage polarization (M1 to M2 phenotype in chronic infection), and subverts dendritic cell maturation (fatima2025epidemiologyaetiologymode pages 11-13, sam2023qfeverimmunology pages 2-3).
Metabolic state: SCVs are metabolically inactive/infectious; LCVs are replicative (fatima2025epidemiologyaetiologymode pages 5-7).
Key host-pathogen interactions: Induction of pro-survival signaling (ERK1/2, AKT), evasion of inflammasome/pyroptosis (IcaA effector) (osbron2022todieor pages 18-19, osbron2022todieor pages 9-9).
Mainly targets: Monocyte, macrophage lineages (CL:0000235), alveolar macrophages (CL:0000584).

7. Anatomical Structures Affected

Primary: Lungs (UBERON:0002048; initial site of entry and infection)
Secondary: Heart (UBERON:0000948; chronic endocarditis), liver (UBERON:0002107; hepatitis), central nervous system (UBERON:0000955 in rare complications; encephalitis, meningitis)
Widespread systemic involvement possible in severe/untreated cases (fatima2025epidemiologyaetiologymode pages 9-11)

8. Temporal Development

Onset: Acutely within 2–3 weeks of exposure (incubation ~20 days)
Progression: 60% asymptomatic; acute symptoms last 2–3 weeks if present. Chronic Q fever can take years to manifest post-exposure, usually as endocarditis or vascular infection (~5% cases).
Course: Acute (self-limited or severe), chronic (progressive, persistent bacteremia/endocarditis), post-infectious fatigue syndrome

9. Inheritance and Population

No Mendelian inheritance; not a genetic disease
Epidemiology:
- EU: 0.2/100,000 annually (christodoulou2023anarrativereview pages 1-2, christodoulou2023anarrativereview pages 4-5)
- Asymptomatic in ~60%, mild symptomatic in ~30–38%, severe requiring admission ~2%, endocarditis in ~5% of infected
- At-risk: Males > females, adults > children, immunocompromised, pregnant
- Endemic in most developed agricultural regions, absent New Zealand

10. Diagnostics

Serology: Phase II IgM/IgG for acute Q fever; Phase I IgG for chronic, particularly endocarditis (fatima2025epidemiologyaetiologymode pages 16-18). Indirect immunofluorescence assay (IFA) is gold standard.
Molecular: PCR for detection (fatima2025epidemiologyaetiologymode pages 16-18)
Culture: Traditional culture infrequently used due to high biosafety requirement (BSL-3)
Other: Imaging for endocarditis/vascular involvement; tissue PCR/histology

11. Outcome/Prognosis

Acute Q fever: Low mortality (~1–2%), complete recovery common
Chronic Q fever: Poorer prognosis, especially with endocarditis; requires prolonged therapy
Q fever fatigue syndrome: Post-infectious persistent fatigue, functional impairment in substantial minority (NCT01318356 chunk 2)

12. Treatment

Treatment	Indication	Regimen	MAXO Term
Doxycycline	Acute Q fever	100 mg twice daily for 14 days (fatima2025epidemiologyaetiologymode pages 16-18)	MAXO:0000647 - antibiotic therapy
Doxycycline + Hydroxychloroquine	Chronic Q fever / Q fever endocarditis	Long-term combination therapy, typically ≥18 months (fatima2025epidemiologyaetiologymode pages 16-18)	MAXO:0000647 - antibiotic therapy
Q-VAX vaccine	Prevention in at-risk populations	Single-dose formalin-inactivated whole-cell vaccine; pre-vaccination screening required (sam2023qfeverimmunology pages 5-6, fatima2025epidemiologyaetiologymode pages 16-18)	MAXO:0001017 - vaccination
Pre-vaccination skin test	Screening before Q-VAX	Intradermal test to identify prior sensitization before vaccination (sam2023qfeverimmunology pages 5-6)	MAXO:0000487
Cognitive behavioral therapy	Q fever fatigue syndrome	Structured CBT program evaluated in the Qure Study (NCT01318356) (NCT01318356 chunk 2)	MAXO:0000199
Valve replacement surgery	Severe endocarditis	Surgical intervention for damaged valves when clinically indicated; used alongside prolonged antimicrobial therapy (fatima2025epidemiologyaetiologymode pages 16-18)	MAXO:0000004

Table: This table summarizes core Q fever treatment and prevention approaches, including acute and chronic antimicrobial regimens, vaccination, screening, and supportive interventions. It is useful for mapping clinical management actions to MAXO ontology terms with supporting citations.

Acute: Doxycycline (100 mg BID × 14 days)
Chronic: Doxycycline + Hydroxychloroquine (≥18 months for endocarditis)
Endocarditis: Combined prolonged antibiotics plus valve surgery as needed
Fatigue syndrome: Cognitive behavioral therapy evaluated (NCT01318356)
Vaccine: Q-VAX (prevention in at-risk, endemic regions)
Prophylaxis: Antibiotic prophylaxis post-exposure highly effective in high-risk settings (fatima2025epidemiologyaetiologymode pages 16-18)

13. Prevention

Human: Q-VAX vaccine (Australia/Russia; formalin-inactivated, screening required for prior sensitization); ongoing development of non-reactogenic, multi-antigen, subunit vaccines—some reaching animal and early clinical study (fatima2025epidemiologyaetiologymode pages 18-20, sam2023qfeverimmunology pages 5-6, jan2023multivalentvaccinesdemonstrate pages 1-3, fatima2025epidemiologyaetiologymode pages 16-18).
Livestock: Coxevac and Chlamyvax FQ in ruminants (fatima2025epidemiologyaetiologymode pages 18-20, sam2023qfeverimmunology pages 5-6)
Infection control: Airborne/droplet precautions in healthcare/lab settings, culling/infection control with livestock, proper disposal of birth products, milk pasteurization
At public health level: Surveillance, notification, occupational risk assessment, vector control policies

14. Other Species / Natural Disease

Reservoirs: Cattle, sheep, goats—primary; others: camels, cats, dogs, horses, rabbits, wild rodents, birds (>100 wildlife species)
Transmission: Major via aerosols from birth products/animal sheds; minor from unpasteurized products; tick vector not essential but involved in maintenance in wild/animal cycles (celina2022coxiellaburnetiiin pages 11-11, celina2022coxiellaburnetiiin pages 1-2, epelboin2023coxiellaburnetiiinfection pages 1-2, fatima2025epidemiologyaetiologymode pages 3-5)
Veterinary Disease: Coxiellosis in livestock, reproductive losses (abortions, stillbirths, infertility)
Comparative Biology: Animal models—guinea pig and mouse for acute Q fever, SCID mice for molecular studies (celina2022coxiellaburnetiiin pages 11-11, zhao2024coxiellaburnetiieffector pages 1-2)

15. Model Organisms

Mouse and guinea pig: Standard for acute Q fever and pathogenesis/vaccine testing
SCID mice: Used for CvpE effector/in vivo replication studies (zhao2024coxiellaburnetiieffector pages 5-7)
Laboratory features: Animals recapitulate human acute, not chronic, manifestations; chronicity/endocarditis models limited (celina2022coxiellaburnetiiin pages 11-11, zhao2024coxiellaburnetiieffector pages 1-2)

16. Immune Response

Innate: Early M1 macrophage polarization with IFN-γ, IL-6, IL-12 production for pathogen kill/survival; in chronic phase, shift to M2 (pro-pathogen) (fatima2025epidemiologyaetiologymode pages 11-13, sam2023qfeverimmunology pages 2-3, sam2023qfeverimmunology pages 2-2)
Adaptive: CD4+ and CD8+ T cells essential; IFN-γ central, as is TNF-α; vaccine-induced immunity is T cell dependent (sam2023qfeverimmunology pages 2-3, sam2023qfeverimmunology pages 12-12, sluder2022evaluationofa pages 16-16)
Evasion: Macrophage reprogramming, IL-10/TGF-β promotion, dendritic cell suppression (fatima2025epidemiologyaetiologymode pages 11-13, sam2023qfeverimmunology pages 12-12)
No established human-borne genetic risk or protective variants

17. Clinical Trials

Key identified ongoing/recent trials: - Q-VAX phase I/II vaccine safety and immunogenicity (NCT02092142; withdrawn) - Q fever fatigue syndrome therapy (NCT01318356; CBT) - Diagnostic screening in pregnancy (NCT01095328) - Seroprevalence and risk factor studies in endemic regions (see context for NCT02898402, NCT03334019, etc.)

18. Drug/Molecular Targets

TRPML1, PIKfyve, CvpE: key molecular targets/mechanisms identified for future host-directed therapies (zhao2024coxiellaburnetiieffector pages 1-2, zhao2024coxiellaburnetiieffector pages 5-7)
No approved direct-acting antivirals or therapies beyond antimicrobials/immune modulation

References

Please see included tables for specific evidence, PubMed IDs, URLs, and publication dates associated with each major claim. All major recent reviews from 2022–2024 and key primary research/data are included herein.

For ontology mapping, suggested terms: - MONDO:0019186 (Q Fever) - HP:0002090, HP:0012115, HP:0001695, HP:0012432, HP:0002383, HP:0001287 (phenotypes) - CL:0000235, CL:0000584 (cell types) - UBERON:0002048, UBERON:0000948, UBERON:0002107, UBERON:0000955 (anatomy) - MAXO:0000647, MAXO:0001017, MAXO:0000487, MAXO:0000199, MAXO:0000004 (medical actions)

For updates and URLs, see these recent key references and their respective DOIs: - doi:10.4236/aid.2025.153035
- doi:10.7759/cureus.38031
- doi:10.3389/fvets.2022.1068129
- doi:10.1038/s41541-023-00727-6
- doi:10.3389/fimmu.2023.1192821
- doi:10.1080/21505594.2024.2350893

References

(OpenTargets Search: Q Fever): Open Targets Query (Q Fever, 0 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(fatima2025epidemiologyaetiologymode pages 3-5): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(christodoulou2023anarrativereview pages 1-2): Magdalini Christodoulou, Foteini Malli, Konstantinos Tsaras, Charalambos Billinis, and Dimitrios Papagiannis. A narrative review of q fever in europe. Cureus, Apr 2023. URL: https://doi.org/10.7759/cureus.38031, doi:10.7759/cureus.38031. This article has 27 citations.
(fatima2025epidemiologyaetiologymode pages 1-3): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(fatima2025epidemiologyaetiologymode pages 5-7): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(fatima2025epidemiologyaetiologymode pages 7-9): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(fatima2025epidemiologyaetiologymode pages 18-20): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(sam2023qfeverimmunology pages 5-6): Gayathri Sam, John Stenos, Stephen R. Graves, and Bernd H. A. Rehm. Q fever immunology: the quest for a safe and effective vaccine. NPJ Vaccines, Sep 2023. URL: https://doi.org/10.1038/s41541-023-00727-6, doi:10.1038/s41541-023-00727-6. This article has 28 citations and is from a peer-reviewed journal.
(fatima2025epidemiologyaetiologymode pages 9-11): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(fatima2025epidemiologyaetiologymode pages 16-18): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(NCT01318356 chunk 2): Stephan Keijmel. The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment. Radboud University Medical Center. 2011. ClinicalTrials.gov Identifier: NCT01318356
(sam2023qfeverimmunology pages 2-2): Gayathri Sam, John Stenos, Stephen R. Graves, and Bernd H. A. Rehm. Q fever immunology: the quest for a safe and effective vaccine. NPJ Vaccines, Sep 2023. URL: https://doi.org/10.1038/s41541-023-00727-6, doi:10.1038/s41541-023-00727-6. This article has 28 citations and is from a peer-reviewed journal.
(zhao2024coxiellaburnetiieffector pages 1-2): Mingliang Zhao, Shan Zhang, Weiqiang Wan, Chunyu Zhou, Nana Li, Ruxi Cheng, Yonghui Yu, Xuan Ouyang, Dongsheng Zhou, Jun Jiao, and Xiaolu Xiong. Coxiella burnetii effector cvpe maintains biogenesis of coxiella-containing vacuoles by suppressing lysosome tubulation through binding pi(3)p and perturbing pikfyve activity on lysosomes. Virulence, May 2024. URL: https://doi.org/10.1080/21505594.2024.2350893, doi:10.1080/21505594.2024.2350893. This article has 8 citations and is from a peer-reviewed journal.
(sam2023qfeverimmunology pages 1-2): Gayathri Sam, John Stenos, Stephen R. Graves, and Bernd H. A. Rehm. Q fever immunology: the quest for a safe and effective vaccine. NPJ Vaccines, Sep 2023. URL: https://doi.org/10.1038/s41541-023-00727-6, doi:10.1038/s41541-023-00727-6. This article has 28 citations and is from a peer-reviewed journal.
(zhao2024coxiellaburnetiieffector pages 5-7): Mingliang Zhao, Shan Zhang, Weiqiang Wan, Chunyu Zhou, Nana Li, Ruxi Cheng, Yonghui Yu, Xuan Ouyang, Dongsheng Zhou, Jun Jiao, and Xiaolu Xiong. Coxiella burnetii effector cvpe maintains biogenesis of coxiella-containing vacuoles by suppressing lysosome tubulation through binding pi(3)p and perturbing pikfyve activity on lysosomes. Virulence, May 2024. URL: https://doi.org/10.1080/21505594.2024.2350893, doi:10.1080/21505594.2024.2350893. This article has 8 citations and is from a peer-reviewed journal.
(fatima2025epidemiologyaetiologymode pages 11-13): Arfiya Fatima and Ravi Kant Upadhyay. Epidemiology, aetiology, mode of transmission and pathogenicity of coxiella burnetii: a review. Advances in Infectious Diseases, 2025. URL: https://doi.org/10.4236/aid.2025.153035, doi:10.4236/aid.2025.153035. This article has 0 citations.
(sam2023qfeverimmunology pages 2-3): Gayathri Sam, John Stenos, Stephen R. Graves, and Bernd H. A. Rehm. Q fever immunology: the quest for a safe and effective vaccine. NPJ Vaccines, Sep 2023. URL: https://doi.org/10.1038/s41541-023-00727-6, doi:10.1038/s41541-023-00727-6. This article has 28 citations and is from a peer-reviewed journal.
(osbron2022todieor pages 18-19): Chelsea A. Osbron and Alan G. Goodman. To die or not to die: programmed cell death responses and their interactions with coxiella burnetii infection. Feb 2022. URL: https://doi.org/10.1111/mmi.14878, doi:10.1111/mmi.14878. This article has 13 citations and is from a domain leading peer-reviewed journal.
(osbron2022todieor pages 9-9): Chelsea A. Osbron and Alan G. Goodman. To die or not to die: programmed cell death responses and their interactions with coxiella burnetii infection. Feb 2022. URL: https://doi.org/10.1111/mmi.14878, doi:10.1111/mmi.14878. This article has 13 citations and is from a domain leading peer-reviewed journal.
(christodoulou2023anarrativereview pages 4-5): Magdalini Christodoulou, Foteini Malli, Konstantinos Tsaras, Charalambos Billinis, and Dimitrios Papagiannis. A narrative review of q fever in europe. Cureus, Apr 2023. URL: https://doi.org/10.7759/cureus.38031, doi:10.7759/cureus.38031. This article has 27 citations.
(jan2023multivalentvaccinesdemonstrate pages 1-3): Sharon Jan, Alycia P. Fratzke, Jiin Felgner, Jenny E. Hernandez-Davies, Li Liang, Rie Nakajima, Algimantas Jasinskas, Medalyn Supnet, Aarti Jain, Philip L. Felgner, D. Huw Davies, and Anthony E. Gregory. Multivalent vaccines demonstrate immunogenicity and protect against coxiella burnetii aerosol challenge. Frontiers in Immunology, Jul 2023. URL: https://doi.org/10.3389/fimmu.2023.1192821, doi:10.3389/fimmu.2023.1192821. This article has 12 citations and is from a peer-reviewed journal.
(celina2022coxiellaburnetiiin pages 11-11): Seyma S. Celina and Jirí Cerný. Coxiella burnetii in ticks, livestock, pets and wildlife: a mini-review. Frontiers in Veterinary Science, Nov 2022. URL: https://doi.org/10.3389/fvets.2022.1068129, doi:10.3389/fvets.2022.1068129. This article has 152 citations and is from a peer-reviewed journal.
(celina2022coxiellaburnetiiin pages 1-2): Seyma S. Celina and Jirí Cerný. Coxiella burnetii in ticks, livestock, pets and wildlife: a mini-review. Frontiers in Veterinary Science, Nov 2022. URL: https://doi.org/10.3389/fvets.2022.1068129, doi:10.3389/fvets.2022.1068129. This article has 152 citations and is from a peer-reviewed journal.
(epelboin2023coxiellaburnetiiinfection pages 1-2): Loïc Epelboin, Mateus De Souza Ribeiro Mioni, Aurelie Couesnon, Mona Saout, Edith Guilloton, Salma Omar, Vincent Pommier De Santi, Bernard Davoust, Jean Lou Marié, Anne Lavergne, Damien Donato, Alexandro Guterres, Sebastien Rabier, Justin Destoop, Felix Djossou, Xavier Baudrimont, Antoine Roch, Gabriel Leonardo Cicuttin, Tatiana Rozental, Mathieu Nacher, Javier Millán, Elba R. Sampaio De Lemos, Jorlan Fernandes, Olivier Duron, Benoit De Thoisy, and Elodie Rousset. Coxiella burnetii infection in livestock, pets, wildlife, and ticks in latin america and the caribbean: a comprehensive review of the literature. Current Tropical Medicine Reports, 10:94-137, Jun 2023. URL: https://doi.org/10.1007/s40475-023-00288-7, doi:10.1007/s40475-023-00288-7. This article has 24 citations and is from a peer-reviewed journal.
(sam2023qfeverimmunology pages 12-12): Gayathri Sam, John Stenos, Stephen R. Graves, and Bernd H. A. Rehm. Q fever immunology: the quest for a safe and effective vaccine. NPJ Vaccines, Sep 2023. URL: https://doi.org/10.1038/s41541-023-00727-6, doi:10.1038/s41541-023-00727-6. This article has 28 citations and is from a peer-reviewed journal.
(sluder2022evaluationofa pages 16-16): Ann E. Sluder, Susan Raju Paul, Leonard Moise, Christina Dold, Guilhem Richard, Laura Silva-Reyes, Laurie A. Baeten, Anja Scholzen, Patrick M. Reeves, Andrew J. Pollard, Anja Garritsen, Richard A. Bowen, Anne S. De Groot, Christine Rollier, and Mark C. Poznansky. Evaluation of a human t cell-targeted multi-epitope vaccine for q fever in animal models of coxiella burnetii immunity. Frontiers in Immunology, May 2022. URL: https://doi.org/10.3389/fimmu.2022.901372, doi:10.3389/fimmu.2022.901372. This article has 20 citations and is from a peer-reviewed journal.

Q Fever

Ask OpenScientist

OpenScientist Report

Pathophysiology

Pathograph

Phenotypes

Medical Actions

Related Datasets

Source YAML

References & Deep Research

Deep Research

1. Disease Information

Synonyms

Key Identifiers

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

16. Immune Response

17. Clinical Trials

18. Drug/Molecular Targets

References

Artifacts