Brucella
Bacteria
- 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 a zoonosis – each Brucella sp is 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.
Transmission
- Contact with raw infected tissue (calving/Dealing with cattle stillbirths) or ingesting undercooked meat.
- Ingestion of unpasteurized dairy products (milk, fresh cheese, cream/ice cream, yoghurt). Refrigeration does not inhibit Brucella's 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).
Test for Brucella
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, 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.
- Brucella PCR also helps in diagnosis.
Monitoring
Monitoring by serology or PCR is difficult as they remain positive despite treatment. Clinical correlation is required.
Brucella clinical picture
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 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.
Complications
(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.
Treatment
- 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.
Bioterrorism
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.
Question
Blood culture from a 7-year-old boy who 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 would you take?
- What treatment advice would you 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.