Diagnostic accuracy of a uniform research case definition for TBM in children: a prospective study.
Bacteriological confirmation of tuberculous meningitis (TBM) is problematic, and rarely guides initial clinical management. A uniform TBM case definition has been proposed for research purposes.



We prospectively enrolled patients aged 3 months to 13 years with meningitis confirmed using cerebrospinal fluid analysis at Tygerberg Hospital, Cape Town, South Africa. Criteria that differentiated TBM from other causes were explored and the accuracy of a probable TBM score assessed by comparing bacteriologically confirmed cases to 'non-TBM' controls.



Of 139 meningitis patients, 79 were diagnosed with TBM (35 bacteriologically confirmed), 10 with bacterial meningitis and 50 with viral meningitis. Among those with bacteriologically confirmed TBM, 15 were Mycobacterium tuberculosis culture-positive and 20 were culture-negative but positive on GenoType(®) MTBDRplus or Xpert(®) MTB/RIF; 18 were positive on only a single commercial nucleic acid amplification test. A probable TBM score provided a sensitivity of 74% (95%CI 57-88) and a specificity of 97% (95%CI 86-99) compared to bacteriologically confirmed TBM.



A probable TBM score demonstrated excellent specificity compared to bacteriological confirmation. However, 26% of children with TBM would be missed due to the limited accuracy of the case definition. Further prospective testing of an algorithm-based approach to TBM is advisable before recommendation for general clinical practice.
Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
R S
RS
Solomons
Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
D H
DH
Visser
Marie Bashir Infectious Diseases and Biosecurity Institute and The Children's Hospital at Westmead, The University of Sydney, Sydney, New South Wales, Australia.
B J
BJ
Marais
Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
J F
JF
Schoeman
Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
A M
AM
van Furth
D000293:Adolescent; D000367:Age Factors; D001431:Bacteriological Techniques; D002555:Cerebrospinal Fluid / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008587:Meningitis, Viral / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000821:virology; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D013019:South Africa; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000382:microbiology