Neurobrucellosis

Brucellosis is a zoonotic infection transmitted to humans from animals (cattle, goats, sheep) via

• direct contact with infected tissues (placenta, aborted foetus), or body fluids (blood, urine),
• contaminated food products, unpasteurised milk or milk products and
• inhalation of aerosols in animal pens, stables, abattoirs and laboratories.

The UK is a non-endemic country. Most brucella cases in the UK are imported cases with links to Mediterranean or Middle Eastern countries. However, Brucella is also endemic in Central Asia, China, South Asia, sub-Saharan Africa, and some parts of Middle and South America.

Clinical presentation

There are three types of neurobrucellosis – meningoencephalitis, diffuse CNS involvement (predominantly myelitis and cerebellar involvement) and polyradiculoneuropathy.

Sign/symptoms

• Headache, fever, myalgia, arthralgia, sweating, back pain.
• Neurologic symptoms include confusion, meningoencephalitis, myelitis, peripheral and cranial neuropathies, and
• psychiatric manifestations (depression, abnormal behaviour, hallucination).

The patient may also have hepatosplenomegaly, hypoesthesia, paraplegia, stroke, brain abscess, and hearing loss.

Investigation:

Neuroimaging – CT/MRI.

All suspected Brucella cases – serum samples should be sent to Brucella Reference Unit (BRU).
The samples are screened using – total brucella antibody assay and specific IgG/IgM enzyme immunoassays.
Screen-positive samples are tested using micro-agglutination assay and PCR when appropriate.
A repeat (convalescent) serum sample could be requested when the antibody titre is non-diagnostic.

Brucella culture confirmation is done in Animal and Plant Health Agency (APHA), Surrey.

Susceptibility test – Not required as there is no evidence of emerging resistance to the common antibiotics used for treatment.

For Neurobrucellosis – BRU requests a serum sample with CSF.
The serum sample is screened first. CSF is only tested if the serum is positive.
CSF test – anti-Brucella antibody or isolation of Brucella.

Laboratory safety

• The laboratory must be notified of the possibility of Brucella as soon as possible. Ideally, the clinician must mention in the request form the possibility of Brucella.
• Specimen from a patient with suspected Brucella infection should be undertaken in the category 3 room. The access to the Category 3 room while processing the specimen should be kept to a minimum. The integrity of the air handling system should be maintained – doors should be closed.
• All manipulation of the isolates of small gram-negative or gram-variable rods within an appropriate safety cabinet.
• Use primary barriers: use safety centrifuge cups, personal protective equipment, and class II or higher Biological Safety Cabinets (BSCs) for procedures with a high likelihood of producing droplet splashes or aerosols.
• Prohibit sniffing of opened culture plates to assist in the identification of isolates.
• Processing should be done by experienced/trained BMS.

Send the isolate to the reference laboratory.

If an organism suggestive of Brucella has been isolated, it must be sent to the Animal and Plant Health Agency (APHA) Brucella Reference Laboratory for identification/confirmation.
APHA must be informed before sending the specimen.
The sample must be packaged following the Health and Safety Executive specifications for Category B infectious substances (UN3373)

Managing potential exposure in the laboratory

Any potential exposure to Brucella must be risk assessed.

Risk assessment can be done with the help of the PHE toolkit
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/700825/Brucella_exposure_assessment_and_flowchart.pdf

Anyone with high-risk exposure, for example –

1. Who has specific risk factors present (sniffing bacteriological cultures, direct skin or mucous membrane contact or present when aerosols are generated)
2. Any individuals who were within 5 feet if the manipulation of Brucella spp. was performed on an open bench,
3. Individuals present in the laboratory during the aerosol-generating process involving Brucella spp.

– should have post-exposure prophylaxis after discussion with the reference unit and Brucella serology tested at 0, 6 and 24 weeks after exposure.

Not pregnant	Doxycycline 100 mg BD for 21 days OR Cotrimoxazole 160/800mg BD for 21 days
Pregnant	Rifampicin 600mg OD for 21 days OR Rifampicin 600mg OD with cotrimoxazole 160/800mg BD and folic acid supplements for 21 days OR Ciprofloxacin 500mg BD for 21 days OR Observation only

Those who might be at risk but not with specific conditions mentioned above should have a baseline serum taken for storage and only be tested with a recent serum if they become symptomatic.

Brucella_exposure_assessment_and_flowchart Download

Treatment

Ceftriaxone plus rifampicin plus doxycycline for 4 -6 weeks, followed by
rifampicin and doxycycline for 12-24 months.

Cotrimoxazole can replace doxycycline or ceftriaxone if any of them is contraindicated.