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.
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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
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
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.
- 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
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
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
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
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
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.
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
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.
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 (endocarditis)
is noted in the description but not modeled in depth here. The infectious_agent
(NCBITaxon) block was omitted at creation and Coxiella burnetii is described in
the text.