Neurobrucellosis
Question:
A 45 years-old Italian farmer visiting the UK has presented to the A&E with severe and persistent headaches, insomnia, neck stiffness, and confusion. His wife mentioned that she had noticed some personality changes and odd behaviour recently. He was having a fever for the last few days but refused to come to the hospital.
He does not have any rash. He drinks alcohol occasionally and is not on any regular medication. He usually is fit and well and does not have any other background diseases.
On questioning, you have found that the farmer and his wife regularly drink unpasteurised milk.
Lumbar puncture was done:
CSF showed -lymphocytosis, increased protein, and decreased glucose levels.
Both Blood culture and CSF culture have grown gram-negative coccobacilli.
What other test(s) would you request?
What advice would you give to the lab?
What advice would you give to the clinicians?
What public health/infection control measures would you take?
Answer (click here)
Other tests:
Serum and CSF to Brucella reference laboratory for serology ( total brucella antibody assay, specific IgG/IgM enzyme immunoassays, micro-agglutination assay) and PCR.
Send the isolate to the Animal and Plant Health Agency (APHA) for identification/confirmation.
It was assumed that this patient already had an initial workup for meningoencephalitis in the form of neuroimaging, haematological and biochemical tests.
Advice to the laboratory:
Inform the laboratory about potential Brucella infection.
Advise to move all the relevant samples and isolate(s) to category 3 room and perform all the procedures inside the safety cabinet as per laboratory protocol.
Inform the laboratory lead/senior BMS.
Help the laboratory perform a risk assessment of potential exposure and arrange for test and post-exposure prophylaxis if appropriate. (See below).
Incident form, RIDDOR if/where appropriate.
Advice to the clinicians
Assess the case and initiate appropriate treatment (Ceftriaxone+rifampicin+ doxycycline).
Keep the clinicians updated about the test results and help with the interpretation of results.
Infection control/Public health
Inform infection control – standard precaution while caring for the patient.
Inform the Public Health team – it is a notifiable disease.
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 product, 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 such as 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 at the 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
Laboratory must be notified of the possibility of Brucella as soon as possible. Ideally clinician must mention in the request form about the possibility of Brucella.
Specimen from a patient with suspected Brucella infection should be undertaken in 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 a 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 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.
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
Anyone with high-risk exposure, for example –
Who has specific risk factors present (sniffing bacteriological cultures, direct skin or mucous membrane contact or present when aerosols are generated).
Individual near (<5 feet) if work on Brucella spp. performed on an open bench,
Individuals present in the laboratory during Brucella spp. aerosol-generating event
– should have post-exposure prophylaxis after discussion with the reference unit and Brucella serology tested at 0, 6 and 24 weeks after exposure.
Brucella_exposure_assessment_and_flowchart.pdfNot 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.
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.