Brucella

Published 8.8.21

• Gram stain – Very small, faintly stained Gram-negative coccobacilli. They tend not to cluster.

• Colonies – Punctate, non-pigmented, and non-haemolytic colonies.

• Brucella grows on blood agar, chocolate agar but not on MacConkey agar.

• Strict aerobe, some strains require carbon dioxide on primary isolation.

• Brucella is non-motile, oxidase-positive, catalase-positive and urease-positive.

There are many Brucella species – not all known to cause human disease. Those known to cause human disease are – B melitensis, B abortus, B suis, B canis and B ceti. Brucella infection is zoonosis – each Brucella sp are associated with some animal host –

• B melitensis: Sheep, goat, Camel (the commonest cause of Brucellosis).

• B abortus: Cattle, Buffalo, Yaks, camels

• B suis: pigs, boar, caribou, rodents

• B canis: canines

• B ceti: Dolphin, whales, porpoise

Brucella survives in the environment for a long time – water (weeks), soil (months).

In animals, they show a predilection for reproductive organs. Brucella is rare in the UK. Most cases are associated with travel to the Mediterranean or Middle Eastern countries.

• Contact with raw infected tissue (calving/Dealing with cattle stillbirths) or ingestion of undercooked meat.

• Ingestion of unpasteurized dairy products (milk, fresh cheese, cream/ice cream, yoghurt). Refrigeration does not inhibit Brucella survival, on the contrary, it lengthens it.

• Inhalation of infected aerosol – protection necessary during aerosol-generating procedures in the laboratory)

• Transmission via blood transmission, transplant, congenital transmission etc (rare).

The infective dose varies based on the species – lowest for B melitensis (1-10) and highest in B canis (approx 10^6).

Culture

All recent Brucella cases in the UK were identified from blood culture. If clinically suspected of Brucella or the blood culture grows small gram-negative bacilli – which are oxidase and/or urease +ve, it should be processed in a containment level 3 facility using a Class I biosafety cabinet.

Standard identification methods like API, MALDI-ToF etc., may misidentify Brucella, and it is recommended to send suspected cultures to the APHA reference laboratory.

Serology

• Screening – Total brucella antibody assay and specific IgG/IgM enzyme immunoassays.

• Micro-agglutination assay
  (B canis is less immunogenic; hence standard screening may not identify B canis infection).

• Serology is to be interpreted based on the clinical information as there are possibilities of false-negative results (in early infection) or false-positive results (due to prior exposure). Repeat serology in 4-6 weeks, and Brucella PCR helps in diagnosis.

Monitoring

Monitoring by serology or PCR is difficult as they remain positive despite treatment. Clinical correlation is required.

Incubation period – weeks to months (usually 1-4 weeks)

• Brucella can cause many different signs/symptoms and has been called the ‘great imitator’.

• It can present as acute infection or chronic infection and, in some cases, asymptomatic infection.

• Common features are – fever, fatigue and arthralgia.

• Brucellosis was previously called undulant fever due to the waxing and waning nature of the fever.

• Other features – Mouldy smelling perspiration, myalgia, anorexia, back pain

• Hepatomegaly, splenomegaly and lymphadenopathy can be seen.

• Haematological features – anaemia, leucopenia/leucocytosis, thrombocytopenia/thrombocytosis, pancytopenia.

Relapse – usually due to non-compliance in up to 15% of cases.

(Focal Brucellosis – organ-related complication)

• CNS infection – meningoencephalitis, radiculoneuropathy, cranial nerve palsy

• Endocarditis, myocarditis, pericarditis, mycotic aneurysm

• Pneumonia, pleural effusion

• Suppurative infection – spleen, liver, lung

• Bone/joint Involvement – sacroiliitis, discitis, arthritis (large joint)

• Pyelonephritis

• Epididymoorchitis.

• Doxycycline+ rifampicin or Doxycycline+aminoglycoside (Streptomycin/gentamicin)

• Combination therapy is preferred.

• A third agent could be added if required – quinolones/cotrimoxazole

• Children – cotrimoxazole+rifampicin, rifampicin+gentamicin, cotrim+ gentamicin

• Other active drugs – quinolones, ceftriaxone

Treatment is usually 6 weeks. May need a longer course in complicated cases e.g. discitis may need 6 months of treatment.

It is a potential agent as the disease can be contracted when inhaled. However, it has low mortality and a long incubation period, which can be considered a disadvantage.

Blood culture from a 7-year-old boy recently returned from Italy has grown this organism – Oxidase +ve, Urease +ve. Clinical details – fever, headache, chills, myalgia, arthralgia (left knee), anaemia, thrombocytopenia.

• What would be your instruction to the lab staff?

• What additional history you would take?

• What treatment advice you would give?

• Whom should you contact?

• What additional tests would you do to get the diagnosis?

Other potential questions –

SAQ: Brucellosis

SAQ: Neurobrucellosis

SAQ: Management of Brucellosis

SAQ: Brucella endocarditis

SAQ: Investigation of Brucella infection

SAQ: Complications of Brucella

SAQ: How would you manage an incident where a laboratory staff was exposed to Brucella.