Brucellosis and Q fever

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Brucella species are small intracellular Gram-negative coccobacilli acquired by ingestion, inoculation or inhalation. B. melitensis, B. abortus and B. suis are mainly travel- or import-associated in the UK, while B. canis can follow contact with infected dogs. Organisms survive within macrophages, enabling relapsing and focal disease.

Coxiella burnetii is an environmentally resistant intracellular bacterium shed by ruminants in enormous concentrations around parturition. Aerosolised organisms travel in dust, so direct animal contact is unnecessary. Acute infection may be febrile, pneumonic or hepatitic; persistent focal infection develops particularly on damaged valves, prosthetic material and abnormal vessels.

Both diseases can present as culture-negative endocarditis, but their diagnostic systems differ. Brucella diagnosis uses exposure-informed cultures, serology and PCR with laboratory biosafety precautions. Q fever uses phase-specific serology and early PCR: phase II responses predominate in acute infection, while high or rising phase I IgG raises concern for persistent focal infection.

Treatment cannot be reduced to one zoonotic regimen. Brucella requires prolonged combination therapy to reduce intracellular relapse. Acute Q fever usually receives doxycycline monotherapy, whereas persistent focal Q fever needs prolonged doxycycline plus hydroxychloroquine, source control where possible and specialist serological follow-up.

Key points

Brucellosis follows unpasteurised dairy, livestock birthing products, abattoir or laboratory exposure, or contact with infected imported dogs, particularly Brucella canis.
Brucellosis commonly causes prolonged or undulating fever, drenching sweats, fatigue, weight loss, arthralgia and hepatosplenomegaly; bone, neurological and cardiac foci must be sought.
Before blood cultures, warn the laboratory that Brucella is suspected; request reference serology and PCR with species-specific exposure details.
Standard smooth-Brucella serology may not detect Brucella canis reliably, so explicitly identify dog exposure and request B. canis testing.
Uncomplicated adult brucellosis is commonly treated with doxycycline 100 mg twice daily plus rifampicin 600 to 900 mg once daily for six weeks under specialist care.
Q fever follows inhalation of Coxiella burnetii-contaminated aerosols, especially from sheep, goats, cattle, placenta, birth fluids, wool, dust or manure.
Acute Q fever causes abrupt fever, severe headache, atypical pneumonia or hepatitis; many infections are asymptomatic.
Persistent focal Q fever most often affects abnormal or prosthetic valves and aneurysmal or grafted vessels; pregnancy is another high-risk setting.
First-line acute Q fever treatment in a suitable non-pregnant adult is doxycycline 100 mg twice daily for 14 days.
Brucellosis is clinician-notifiable in England; Brucella species and Coxiella burnetii are laboratory-notifiable organisms, and clusters or occupational hazards need health-protection input.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Livestock Brucella

B. melitensis, B. abortus and B. suis are acquired through unpasteurised dairy, infected tissues, aerosols or occupational inoculation.

Canine brucellosis

B. canis can pass from infected dogs, reproductive fluids or laboratory material and requires assay-specific diagnostic consideration.

Coxiella aerosols

C. burnetii concentrates in ruminant placenta and birth fluids, contaminating wool, manure, dust and downwind environments.

Occupational risk

Farmers, veterinarians, abattoir staff, animal breeders and laboratory workers have increased exposure to both pathogens through distinct routes.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Macrophage survival
Brucella enters phagocytes and modifies intracellular trafficking, allowing reticuloendothelial persistence, bacteraemic relapse and seeding of focal sites.
2
Osteoarticular tropism
Brucella commonly seeds sacroiliac joints, vertebral endplates and other synovial structures, producing chronic inflammation and abscess.
3
Coxiella intracellular replication
C. burnetii replicates within acidic phagolysosome-like vacuoles and resists environmental stress in a durable small-cell form.
4
Persistent focal infection
Coxiella localises on abnormal valves, aneurysms and vascular grafts where low-grade infection produces immune-complex and embolic complications.
5
Placental amplification
Both organisms can infect reproductive tissues, while Coxiella reaches especially high burden in placenta and birth products.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Brucella systemic illness

Undulating fever, drenching or malodorous sweats, fatigue, anorexia, weight loss, headache and diffuse arthralgia can persist for weeks.

Brucella focal diseaseRed flag

Sacroiliitis, spondylodiscitis, peripheral arthritis, epididymo-orchitis, hepatosplenic lesions, neuroinfection and endocarditis explain localising symptoms or relapse.

Acute Q fever

Abrupt high fever, severe headache, myalgia, dry cough, pneumonia or hepatitis follows livestock aerosol exposure, although infection may be asymptomatic.

Persistent focal Q feverRed flag

Months of fever, fatigue, weight loss, valve dysfunction, vascular pain or emboli can follow apparently mild or unrecognised acute infection.

Pregnancy-associated infectionRed flag

Maternal illness may be mild while placental infection causes miscarriage, stillbirth, fetal growth restriction or preterm delivery.

Occupational or cluster patternRed flag

Linked illness among farm, veterinary, abattoir or laboratory workers can reveal an aerosol or animal-source exposure requiring health-protection investigation.

Red flags requiring action

A new murmur, heart failure, embolic signs or persistently raised inflammatory markers suggests Brucella endocarditis or persistent focal Q fever.
Severe headache, meningism, cranial neuropathy, confusion, myelopathy or focal weakness may be neurobrucellosis or Q fever neurological disease.
Back pain, focal bony tenderness, painful hip or sacroiliac joint can indicate Brucella spondylodiscitis or osteoarticular infection.
Known vascular aneurysm, prosthetic graft or valvular disease increases the risk and consequence of persistent focal Q fever.
Pregnancy with either infection requires urgent obstetric and infection input because fetal loss, preterm birth and placental infection can occur.
Tell the microbiology laboratory before handling cultures from suspected brucellosis because aerosol-generating work can infect laboratory staff.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Exposure and focal-risk historyFirst step
Why
Separate Brucella from Q fever and identify persistent-infection risk before selecting tests.
Interpretation and limitations
Ask about countries, unpasteurised dairy, livestock species, birthing products, abattoir or laboratory work, imported dogs, valve disease, aneurysm, vascular graft and pregnancy.
02
Blood cultures with laboratory warning
Why
Recover Brucella and other causes of prolonged fever or endocarditis safely.
Interpretation and limitations
Take multiple sets before antibiotics when this causes no dangerous delay, label suspected Brucella and telephone microbiology so prolonged incubation and biosafety precautions are used.
03
Brucella reference serology
Why
Support diagnosis when culture is negative or antibiotics have already been given.
Interpretation and limitations
Interpret titre and change over time with symptoms and epidemiology; cross-reaction and persistent antibodies limit isolated results, and routine smooth-antigen assays can miss B. canis.
04
Brucella PCR
Why
Detect organism DNA in blood or focal samples and support species-level investigation.
Interpretation and limitations
Discuss specimen choice with the Brucella Reference Unit; a negative blood PCR does not exclude focal disease and PCR is not a simple test of cure.
05
Q fever PCR
Why
Directly detect C. burnetii during early acute illness before or around seroconversion.
Interpretation and limitations
Sensitivity falls after antibiotics and as antibodies emerge; notify the reference laboratory of illness day, pregnancy and suspected cardiac or vascular focus.
06
Q fever phase-specific serology
Why
Diagnose acute infection and identify a pattern requiring persistent focal infection assessment.
Interpretation and limitations
Phase II antibodies usually dominate acute infection; high or rising phase I IgG is concerning but must be combined with echocardiographic, vascular and clinical evidence.
07
Echocardiography
Why
Assess endocarditis when either zoonosis causes persistent fever, emboli, murmur or valve-risk features.
Interpretation and limitations
Start with transthoracic imaging and use transoesophageal echocardiography when suspicion remains; Q fever vegetations may be small or absent, so negative imaging does not exclude disease.
08
Focal imaging and baseline safety tests
Why
Locate osteoarticular, vascular, hepatosplenic or neurological infection and prepare for prolonged treatment.
Interpretation and limitations
Use MRI for spine or neuroaxis, CT or PET-CT for selected vascular or occult foci, and obtain FBC, renal, liver, ECG and ophthalmic baselines as the regimen requires.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Tuberculosis

Prolonged fever, sweats, weight loss, lymphadenopathy and spinal disease overlap, requiring site-specific imaging, culture and molecular testing.

Culture-negative endocarditis

Bartonella, fungi, prior antibiotic exposure and non-infective endocarditis compete with Brucella and Coxiella explanations and require exposure-led testing.

Enteric fever or malaria

Travel-associated fever and splenomegaly demand blood cultures and urgent malaria films even when zoonotic exposure is convincing.

Malignancy or inflammatory disease

Lymphoma, vasculitis, sarcoidosis and connective-tissue disease can cause fever, weight loss, cytopenia and organ inflammation without a zoonotic infection.

Other atypical pneumonia

Legionella, psittacosis and respiratory viruses resemble acute Q fever; water, bird, livestock and outbreak histories guide testing.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01BRUCELLAProtect the laboratory and define the focusFirst stepProlonged fever follows unpasteurised dairy, livestock, abattoir, laboratory or infected-dog exposure.

1Record species, product, country, dates and occupational contacts, then examine joints, spine, liver, spleen, testes, nervous system and heart.
2Telephone microbiology before culture processing, obtain multiple blood cultures and send reference serology and PCR as advised.
3Request B. canis-specific assessment when dog breeding, imported dogs, reproductive tissue or a known canine case is relevant because routine serology may miss it.
4Image localising symptoms and obtain echocardiography when fever is prolonged, cultures persist or cardiac features are present.

02TREAT BRUCELLAUse prolonged combination therapyAdult brucellosis is clinically and microbiologically supported.

1For uncomplicated disease, give doxycycline 100 mg orally twice daily plus rifampicin 600 to 900 mg orally once daily for six weeks under infection-specialist oversight.
2Check pregnancy, allergies, liver function, interactions and adherence before treatment; rifampicin reduces exposure to many medicines including hormonal contraception and anticoagulants.
3For endocarditis, neurobrucellosis, spondylodiscitis or other deep focus, add or substitute an aminoglycoside and extend therapy according to specialist and surgical assessment.
4Investigate relapse with repeat cultures and focal imaging rather than simply repeating the same course without understanding the source.

03ACUTE Q FEVERConfirm early and treat suitable adultsAcute fever, pneumonia or hepatitis follows a plausible ruminant or environmental aerosol exposure.

1Send early blood for C. burnetii PCR and acute serology, then arrange convalescent phase-specific serology if the first sample is non-diagnostic.
2Give doxycycline 100 mg orally twice daily for 14 days to a suitable non-pregnant adult, starting on clinical suspicion when illness is significant.
3Use specialist-selected alternatives during pregnancy or when doxycycline is contraindicated; do not improvise a short generic pneumonia course.
4Assess baseline valve, vascular and pregnancy risk because these determine follow-up for persistent focal infection after acute symptoms resolve.

04PERSISTENT Q FEVERFind and treat the infected focusPhase I antibodies are high or rising, symptoms persist, or valve, aneurysm, vascular graft or pregnancy risk is present.

1Involve infection, cardiology and vascular specialists, repeat phase-specific serology and use echocardiography plus vascular imaging or PET-CT according to the suspected focus.
2Use doxycycline 100 mg twice daily plus hydroxychloroquine 200 mg three times daily under specialist monitoring, commonly for at least 18 months for native-valve and 24 months for prosthetic-valve infection.
3Check G6PD status, ECG, renal and liver function, baseline retinal status, hydroxychloroquine concentration where available and serial phase I titres.
4Discuss valve or infected vascular-material surgery when structural damage, heart failure, uncontrolled infection, embolic risk or graft involvement makes medicines alone inadequate.

05PUBLIC HEALTHNotify and control the sourceEither infection is suspected, confirmed, occupationally acquired or linked to a cluster.

1Notify suspected brucellosis promptly under the England clinician duty and ensure Brucella or C. burnetii laboratory notifications proceed through the diagnostic service.
2Contact the health-protection team about clusters, occupational exposure, UK acquisition, laboratory exposure or ongoing livestock and food hazards.
3Advise against unpasteurised milk and cheese, and involve veterinary, food-safety or workplace teams rather than attempting animal-source management clinically.
4Use appropriate precautions for birth products and infected animal tissues; routine household isolation is not required because ordinary person-to-person spread is rare.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Standard oral combination that reduces relapse compared with inadequate monotherapy.

Doxycycline plus rifampicin

Give doxycycline 100 mg orally twice daily plus rifampicin 600 to 900 mg orally once daily for six weeks for uncomplicated adult brucellosis under specialist supervision.

Avoid routine doxycycline in pregnancy, check hepatic function and major rifampicin interactions, counsel that rifampicin discolours secretions and reduces hormonal-contraceptive effectiveness, and reinforce full-course adherence.

Adds rapid bactericidal activity for complicated or deep focal brucellosis.

Aminoglycoside-containing brucellosis regimen

Use gentamicin or streptomycin at weight- and renal-function-adjusted specialist doses alongside doxycycline-based therapy for selected endocarditis, neurobrucellosis, spondylodiscitis or severe disease.

Monitor creatinine, drug concentrations, hearing and vestibular toxicity; pregnancy, renal impairment and prolonged courses require an individually selected alternative.

First-line treatment for acute febrile, pneumonic or hepatitic Q fever in suitable adults.

Doxycycline for acute Q fever

Give 100 mg orally twice daily for 14 days to a suitable non-pregnant adult with acute Q fever, beginning promptly when the syndrome is convincing.

Avoid routinely in pregnancy and children under 12 years, counsel on photosensitivity and oesophagitis, separate from cations, and use infection-specialist advice for severe disease or contraindications.

Prolonged combination therapy for endocarditis or vascular infection; hydroxychloroquine alkalinises the intracellular compartment and improves doxycycline activity.

Doxycycline plus hydroxychloroquine

Give doxycycline 100 mg twice daily plus hydroxychloroquine 200 mg three times daily for specialist-confirmed persistent focal Q fever, usually for at least 18 to 24 months depending on focus.

Specialist-only regimen: check QT risk, retinal status, G6PD, renal and liver function, drug interactions and hydroxychloroquine exposure; pregnancy requires a separately agreed plan.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Endocarditis

Valve infection causes heart failure, emboli and death; Brucella and Coxiella are important causes of culture-negative disease.

Osteoarticular brucellosis

Sacroiliitis, spondylodiscitis and peripheral arthritis can cause abscess, neurological compression, spinal instability, chronic pain and prolonged functional disability.

Neurobrucellosis

Meningitis, encephalitis, myelitis, radiculopathy or cranial neuropathy may produce lasting neurological impairment without extended specialist treatment.

Q fever vascular infection

Infection of aneurysms or prosthetic grafts can cause expansion, fistula, rupture, embolisation and persistent bloodstream inflammation.

Adverse pregnancy outcome

Placental infection increases miscarriage, stillbirth, fetal growth restriction and prematurity, sometimes despite limited maternal symptoms or apparently mild acute illness.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

For brucellosis, review fever curve, focal pain, examination, cultures, FBC, CRP, renal and liver profiles during therapy and for relapse after completion.
Monitor rifampicin interactions actively, including anticoagulants, antiretrovirals, transplant medicines, anticonvulsants and hormonal contraception, rather than relying on a one-time check.
For aminoglycosides, use local therapeutic drug monitoring with serial renal, auditory and vestibular assessment.
After acute Q fever, arrange specialist follow-up for people with valvular disease, vascular aneurysm or graft, immunosuppression or pregnancy because persistent focal infection may be initially silent.
During persistent Q fever treatment, trend phase I serology, symptoms, inflammatory markers and organ imaging; titres support but do not replace clinical assessment.
Monitor hydroxychloroquine with baseline and interval ophthalmology, ECG when QT risk exists, renal and liver profiles, interactions and specialist drug concentrations where available.
Document occupational and source-control actions, including exposed-worker advice and veterinary or environmental investigation outcomes.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Warn before culturing Brucella

Laboratory-acquired brucellosis follows aerosol exposure, so a phone call and clear specimen labelling are clinical safety interventions.

Dog exposure changes the assay

Brucella canis lacks the smooth lipopolysaccharide targeted by standard assays, making exposure-specific reference testing essential.

Q fever needs no direct contact

Coxiella survives in dust and travels on air currents, so residence near parturient livestock can be sufficient exposure.

Phase is not simply timing

Q fever phase I and II refer to antigenic forms; phase-specific antibody patterns help distinguish acute from persistent focal infection.

Endocarditis may be echocardiographically quiet

Coxiella vegetations may be tiny or absent, so valve risk, serology and systemic evidence remain important despite negative imaging.

Scope boundary

Organism-specific diagnostics and regimens are detailed here; generic endocarditis, spinal infection, meningitis and pregnancy pathways continue alongside them.

11Common pitfallsFrequent interpretation and management errors.

01
Do not let a possible Brucella culture enter routine laboratory processing without telephoning microbiology and stating the exposure.
02
Do not use standard Brucella serology alone to exclude B. canis after a relevant dog exposure.
03
Do not treat brucellosis with an inadequately short or single-drug regimen because intracellular persistence drives relapse.
04
Do not diagnose persistent Q fever from one antibody titre without looking for a cardiac, vascular or other focal infection.
05
Do not exclude Q fever endocarditis because routine blood cultures and transthoracic echocardiography are negative.
06
Do not use doxycycline casually during pregnancy; urgent specialist selection must balance maternal and fetal risks.
07
Do not confuse the clinician notification list with the laboratory organism list; brucellosis and Coxiella have different statutory routes.