What is the sensitivity and specificity of cerebrospinal fluid (CSF) tests for Brucella infection?

Sensitivity and Specificity of CSF Tests for Brucella Infection

For diagnosing neurobrucellosis, CSF serology tests have high specificity (>95%) but variable sensitivity, while CSF culture has high specificity (>99%) but low sensitivity (30-70%). 1

Diagnostic Tests for Neurobrucellosis

CSF Serology Tests

• Brucella agglutination tests in CSF show positive results in most neurobrucellosis cases, though titers are typically lower in CSF than in serum 2
• Coombs test is more sensitive than standard agglutination tests, with consistently positive results in both serum and CSF of neurobrucellosis patients 3
• ELISA and indirect immunofluorescent tests on CSF provide additional diagnostic value with higher sensitivity than standard agglutination 4

CSF Culture

• CSF culture has high specificity (>99%) but limited sensitivity, with positive results in approximately 30-70% of neurobrucellosis cases 2, 3
• In one study, Brucella melitensis was isolated from CSF in only 4 out of 7 confirmed cases (57% sensitivity) 3
• Another study showed isolation of Brucella melitensis from CSF in 3 out of 6 culture-positive cases (50% of culture-positive cases had positive CSF cultures) 4

CSF PCR

• While not specifically validated for Brucella in the guidelines, PCR techniques show promise for diagnosis of bacterial meningitis with reported sensitivity of 94-100% and specificity of 96-98.2% for bacterial pathogens in general 1
• Metagenomic next-generation sequencing of CSF has been successfully used to diagnose neurobrucellosis in cases where conventional methods were inconclusive 5

CSF Findings in Neurobrucellosis

• Typical CSF abnormalities include:
  • Lymphocytic pleocytosis 2, 3
  • Elevated protein levels (>100 mg/dL in many cases) 2, 3
  • Low glucose (hypoglycorrhachia) 2, 3
  • Increased gamma-globulin and IgG values with oligoclonal bands 3

Diagnostic Algorithm for Suspected Neurobrucellosis

1. Obtain CSF for:

   • Standard analysis (cell count, protein, glucose)
   • Brucella serology (agglutination tests and Coombs test)
   • Culture
   • Consider PCR if available 1, 4

2. Obtain serum for parallel Brucella serology testing 4, 2

3. Interpret results:

   • Positive CSF culture confirms diagnosis with high specificity 2
   • Positive CSF serology with typical CSF findings and compatible clinical picture strongly supports diagnosis even with negative cultures 3
   • Positive serum serology with negative CSF results does not rule out neurobrucellosis 3

Clinical Pearls and Pitfalls

• CSF cultures may remain negative despite active neurobrucellosis, especially if antibiotics were administered prior to sampling 2
• Low or absent agglutination titers in CSF do not exclude neurobrucellosis; Coombs test is more reliable 3
• After successful treatment, CSF may continue to show positive Coombs test at low titers and elevated gamma-globulin/IgG levels despite clinical cure 3
• White matter lesions on neuroimaging should prompt consideration of neurobrucellosis in endemic areas, with appropriate CSF testing 6
• Neuroimaging may be normal in up to 25% of neurobrucellosis cases despite positive CSF findings 6