Brucella: laboratory and clinical services
The Brucella Reference Unit (BRU) provides laboratory diagnostic and clinical management services for Brucella species.
The BRU provides:
- advice on the diagnosis and clinical management of brucellosis
- assistance in the diagnosis of neurobrucellosis
- a Brucella serodiagnosis service
Likelihood of brucellosis in a UK patient
Brucellosis is a rare disease in the UK as it is a non-endemic country. Typically, most patients will have been exposed to infection in a Mediterranean or Middle Eastern country, but the range of countries with risk is changing. A detailed travel history is vital. Use BRU’s serology referral form and provide as much clinical detail as possible.
Diagnostic services
The BRU provides a Brucella serodiagnosis service and tests are performed weekly.
If there is a clinical urgency, please contact Liverpool Clinical Laboratories on 0151 706 4410.
Use the Brucella serology referral form.
Laboratory tests
The laboratory uses a range of commercial CE-marked and both in-house assays to detect both total IgG, IgM and specific IgG and IgM brucella antibodies. All sera are screened using a CE-marked total brucella antibody assay and specific IgG/IgM enzyme immunoassays. Screen positive samples undergo further testing with an in-house micro-agglutination assay.
If the serology titres suggest possible active infection, samples are tested for Brucella PCR. This test is a pan-genus assay and is unable to differentiate between species of Brucella. A minimum of 500ul of serum is required.
The screening tests used at BRU are very sensitive (low false negative rates). However, if there is a strong clinical suspicion of brucellosis, it is good practice to repeat the test after a 6 week period.
Interpretation of serological test results
Approximately 95% of sera received by BRU are seronegative in all screening tests. The remaining 5% of brucellosis serology results need to be interpreted with caution because of possible false negative results (in early infection) or false positive results (due to prior exposure).
At BRU, interpretation of Brucella antibody titres is based on:
- the availability of relevant clinical information, see Brucella serology referral form)
- a low clinical threshold to request a follow up serum in 4 weeks’ time if a serum sample is considered to have non-diagnostic antibody titres
- results of Brucella PCR where appropriate
Culture confirmation
The BRU does not provide a culture confirmation service, but collaborates closely with the OIE/FAO Reference Laboratory for Brucellosis at the Animal and Plant Health Agency (APHA) in Surrey, to whom all suspect culture isolates should be sent.
For further information on the referral of suspected Brucella cultures or clinical material, please contact the Brucella Reference Laboratory by email at BrucellaGroup@apha.gov.uk or by telephone on 0330 041 6562.
Antimicrobial sensitivity testing
This is not required as there is no evidence that antimicrobial resistance has emerged to the standard agents used in the treatment of human brucellosis.
Molecular tests for brucellosis
Brucella PCR is available at BRU and is routinely tested on samples that show serology compatible with possible active infection. PCR can also be performed on request – please discuss with BRU if there is a high clinical suspicion of infection. A minimum of 500ul of serum is required for this test.
Monitoring response to treatment
Serological testing is not useful for this as Brucella antibody titres fall slowly after treatment. Follow-up serology therefore requires careful interpretation.
Brucella PCR can also remain positive despite successful treatment, and therefore needs to be correlated clinically.
Neurobrucellosis
This is a very rare condition in the UK. Negative serology should exclude the diagnosis so always send a serum sample in the first instance. Cerebrospinal fluid (CSF) will only be examined for Brucella antibody if there is evidence of Brucella seroreactivity in serum.
Diagnosis of Brucella canis infection
Brucella canis is the cause of brucellosis in dogs. It is not usually present in British dogs but may occur in dogs imported from other countries. The origin and travel history of implicated animals should be checked.
This species of Brucella lacks surface lipopolysaccharide (LPS) and therefore will elicit a minimal anti-LPS immunological response, hence suspected B. canis infection will not be identified by standard Brucella antibody screening tests. Consequently, B. canis serology should be specifically requested on the request form if infection due to this species is suspected.
Marine mammal brucellosis
Two Brucella species, B. ceti and B. pinnipedialis, have been isolated from marine mammals. Cetaceans (dolphins and similar animals), seals and sea lions are the preferred hosts. A few human cases have been reported with naturally acquired infection with marine species of Brucella.
No precautions specific to these species can currently be advised, however brucellosis should be considered if the patient becomes unwell after exposure. It is important to note that our serology tests may not detect marine brucellosis species.
Advice on diagnosis and clinical management
Please contact:
Liverpool Clinical Laboratories
Virology Department
8th Floor, Duncan Building
Royal Liverpool and Broadgreen Hospital
Prescot Street
Liverpool
L7 8XP
Email BrucellaQueries@liverpoolft.nhs.uk
Laboratory switchboard: 0151 706 4410
Antibiotic management of brucellosis in children
Management should always be overseen by a consultant paediatrician with a specialist interest in infectious diseases. In the absence of randomised controlled trials, the guidance published by the American Academy of Paediatrics is recommended. This includes dosage guidance:
- 12 years of age or older: oral doxycycline plus rifampicin for 6 weeks
- for younger children, cotrimoxazole may be used instead of doxycycline but we recommend early consultation with BRU in all cases to determine best individualised care
For patients with osteoarticular disease, neurobrucellosis or endocarditis, referral to a specialist paediatric infectious disease unit is recommended as aminoglycoside therapy is usually indicated.
Laboratory exposures
Staff in routine diagnostic laboratories are not normally considered to be at risk of infection with Brucella. Blood from patients with brucellosis will have a very low level bacteraemia and should not pose a risk during routine processing in haematology, clinical chemistry or blood sciences laboratories. Rare instances of high risk exposures such as a blood conjunctival splash might require discussion with BRU. Otherwise, staff do not need monitoring or testing.
However, in the event of an exposure to a Brucella culture, risk assessment and follow up is required.
The following good practice guidelines are recommended in order to avoid laboratory exposures occurring:
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when brucellosis is suspected, clinicians should note the suspicion of brucellosis on the laboratory request form; however, as clinical details are often insufficient to identify high risk specimens when received in the laboratory, all blood cultures should be assessed for risk of Category 3 organisms and handled appropriately
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almost all Brucella isolates in the UK over the past 5 years have been isolated only from blood culture; that is why all unusual small Gram-negative or Gram-variable rods from blood culture which are either oxidase positive or urease positive, or both, should be examined in a containment level 3 facility using a Class I biosafety cabinet
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note that current laboratory identification methods (such as API®, VITEK®, MALDI-TOF) may not give reliable identification of suspect isolates with both false positive and false negative results occurring; all suspect isolates should be confirmed at the APHA reference laboratory
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the most common mode of laboratory exposure to Brucella is handling and sniffing plates with suspect isolates on an open bench; this should be discouraged
For further information on the referral of suspected Brucella cultures or clinical material, please contact the Brucella Reference Laboratory by email at BrucellaGroup@apha.gov.uk or by telephone on 0330 041 6562.
Urine samples
Patients with brucellar epididymo-orchitis are typically diagnosed on the basis of positive blood cultures or serology, or both. It is uncommon for urine analysis to show abnormalities. On occasions, Brucella species can be cultured from urine but the yield is low and this is not usually attempted. However, routine urine cultures should be taken in all patients to rule out other aetiologies.
A typical laboratory exposure to urine would not normally be regarded as constituting a significant hazardous exposure. However, a high risk exposure (for example, a conjunctival splash) of urine from an untreated patient with urinary tract involvement might be an exception to this rule. In such cases, ring BRU for advice on risk assessment.
Surgical exposure risks in patients with active brucellosis
| Clinical scenario | Risk | PPE |
|---|---|---|
| Pregnancy and delivery | Infective products of conception or placenta | Aerosol precautions and standard precautions (FFP3 masks, gown, gloves, eye goggles or visor) |
| Procedures on Brucella septic arthritis | Aerosol generation especially during inoculation of pressurised containers | Aerosol precautions and standard precautions (FFP3 masks, gown, gloves, eye goggles or visor) |
| Procedures on Brucella abscess | Aerosol generation especially during inoculation of pressurised containers | Aerosol precautions and standard precautions (FFP3 masks, gown, gloves, eye goggles or visor) |
Recommendations and precautions for blood donations
Patients who have previously had a clinical diagnosis of brucellosis should not donate blood.
Patients who have had a high risk exposure to brucellosis (usually in the context of a laboratory exposure) should have serology testing before donating blood.
Further guidance and forms
- procedure for managing laboratory exposure, including factsheet
- veterinary exposure factsheet
- Brucella serology referral form (Y3)
- Brucella culture referral form (B1)
Contact BRU
Brucella Reference Unit
Liverpool Clinical Laboratories
Virology Department
8th Floor, Duncan Building
Royal Liverpool and Broadgreen Hospital
Prescot Street
Liverpool
L7 8XP
Medical and technical enquiries: 0151 706 4410
Last updated 16 June 2023 + show all updates
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Updated contact details.
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Added information under Laboratory tests, Interpretation of serological test results, Molecular tests for brucellosis, Monitoring response to treatment. Updated contact details for advice on diagnosis and clinical management. Added link to Brucella culture referral form.
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APHA laboratory phone number updated
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Added contact details for Dr Alessandro Gerada.
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Contact details for APHA reference laboratory changed.
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Updated with more details of services provided by BRU.
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First published.