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.

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.

See HAIRS risk assessment

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:

Email: BrucellaQueries@liverpoolft.nhs.uk

Laboratory switchboard: 0151 706 4410