Investigations
1st investigations to order
blood culture
Test
Considered the mainstay of diagnosis.[90] The sensitivity of blood cultures depends largely on previous antibiotic use, the phase of the disease, and the method of culturing.[91][92][93]
Traditional culture sensitivity is improved by using sensitive methods such as lysis-centrifugation or specialised culture media (e.g., Castañeda's medium) and by extending culture duration to 6 weeks. Modern culture systems are more sensitive and usually become positive within 1 week, but subcultures should be maintained for up to 3 weeks.[93][Figure caption and citation for the preceding image starts]: Small pearly-white colonies of Brucella melitensis after prolonged culture on blood agarFrom the collection of Dr Nicholas J. Beeching; used with permission [Citation ends].
Result
positive growth of Brucella species
serological tests
Test
Cultures are not always available or successful, so patients are usually investigated using at least one serological test, typically an agglutination test or enzyme-linked immunosorbent assay (ELISA). Serological tests are still based on the traditional (Wright) standard agglutination test (SAT) or tube agglutination test (TAT), modified in some laboratories to be performed in small ELISA plates as the microagglutination test (MAT).[94]
The techniques suffer from lack of standardisation and are notoriously affected by the prozone phenomenon, caused by blocking IgA antibodies, yielding false negative results at low dilutions of patient serum.[1]
ELISA tests usually have high sensitivity but variable specificity.[84][94][96]
Rose Bengal agglutination tests, developed for veterinary practice, are used in some countries to screen human sera but require subsequent confirmatory testing.[95][94]
There is considerable cross-reactivity between Brucella species, as well as with other gram-negative bacteria; therefore, species diagnosis by serology is not reliable.[98]
Rapid point-of-care serological assays have been developed but require further evaluation before introduction into routine practice.
Routine serological tests are not effective for diagnosing or monitoring infection with B canis or with RB51 (the B abortusstrain used in animal vaccines).[77] Using a combination of serological tests may overcome the current limitations of testing.[120]
Result
positive agglutination titre of ≥160, or a fourfold or greater rise in titre between samples taken 2 weeks apart
cerebrospinal fluid (CSF) analysis
Test
Lumbar puncture is indicated in patients with neurological signs and symptoms to exclude meningoencephalitis. Serological tests on CSF are difficult to interpret, but the standard agglutination test is usually positive.[1][108][109]
Result
lymphocyte predominance with mildly raised protein and reduced or borderline glucose levels
cerebrospinal fluid (CSF) culture
Test
Rarely positive, but is improved by use of automated culture systems.[109]
Result
may show positive growth of Brucella species
synovial fluid analysis
Test
Indicated in all patients with joint effusion.
Result
lymphocyte predominance with raised protein and reduced glucose levels in cases of arthritis
synovial fluid culture
Test
Indicated in all patients with joint effusion. Frequently positive.
Result
positive growth of Brucella species
FBC
liver function tests
serum electrolytes
Test
Hyponatraemia, associated with SIADH, has been reported in patients with brucellosis.[113] May also reveal other electrolyte derangements.
Result
hyponatraemia
Investigations to consider
bone marrow culture
Test
Bone marrow cultures have a greater positive yield than blood cultures, as the organism is intracellular and localised in the bone marrow, and may be considered in difficult cases (e.g., negative blood cultures, negative serology, and brucellosis suspected).[91]
Result
positive growth of Brucella species
tissue biopsy
Test
Clinically affected organs and tissues can be biopsied, particularly lymph nodes, liver, and, occasionally, synovium. This is partly to obtain material for culture to exclude tuberculosis.
Result
non-caseating granulomata
plain film x-rays of affected joints
Test
These changes in the axial skeleton and peripheral joints occur late in the disease.[1]
Result
small erosions near affected joints, moderate sclerosis of bone adjacent to infected joints, and little joint destruction or loss of joint space
chest x-ray
Test
Findings typically normal. Reserved for patients with pulmonary signs and symptoms.[88]
Result
normal, or pleural effusion and consolidation
bone scan
Test
Sensitive and may reveal subclinical joint infection.[115]
This study may be of use early in the disease, when abnormalities are usually not visible on plain film radiographs, and should be considered for patients with musculoskeletal manifestations. Furthermore, bone scan may help distinguish hip involvement from sacroiliitis.
Result
variable
CT or MRI scan of spine
Test
Useful for delineating infection of the spine and paraspinal tissues.
Result
variable
CT or MRI scan of head
Test
Rare findings in cases of central nervous system infection.
Result
may show intracranial collections, calcification, or hydrocephalus
Emerging tests
polymerase chain reaction (PCR) for detection and diagnosis of Brucella species
Test
Usually more rapid than culture and has sensitivity reported to approach 100%, with a specificity of 98.3%.[102]
May be particularly useful in patients with relapse or re-infection and has been used in trials to monitor progression of treated patients and assess relapse.[103]
However, PCR methods are still not standardised, are susceptible to contamination, and have yielded contradictory results with prolonged positivity in some settings, so their full potential has yet to be realised.[104]
Result
positive
matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry
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