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.
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.
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 in-house micro-agglutination and complement fixation in-house assays.
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
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 referral of suspected Brucella cultures, please contact Lorraine Perrett by email at: Lorraine.Perrett@apha.gsi.gov.uk or by telephone on 0208 026 9840.
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
Please discuss with BRU staff.
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.
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 either:
Dr Nick Beeching
Senior lecturer (clinical) in infectious diseases
Royal Liverpool University Hospital (RLUH)
Telephone (direct dial) 0151 706 3836
RLUH switchboard 0151 706 2000
Dr Pankaj Lal
Consultant medical microbiologist and honorary senior clinical lecturer in medical microbiology
Royal Liverpool University Hospital (RLUH)
Telephone (direct dial) 0151 529 4916
RLUH switchboard 0151 706 2000
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.
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:
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
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
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.
For further information on referral of cultures, please contact Lorraine Perrett Lorraine.Perrett@apha.gsi.gov.uk or by telephone: 0208 026 9840
- 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
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
|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 reference unit
Liverpool Clinical Laboratories
Royal Liverpool and Broadgreen University Hospital NHS Trust
Medical enquiries 44 (0)151 529 4916
Technical enquiries 44 (0)151 706 4410