Heemskerk 2018.

Study characteristics
Patient Sampling	Cross‐sectional, consecutive, prospective
Patient characteristics and setting	Presenting signs and symptoms: patients who were offered lumbar puncture as a part of routine care for suspected brain infection Age: ≥ 18 years; median 37 years (IQR 28 to 50) Sex, female: 43% Children: no HIV infection: 31% Clinical setting: multicentre, hospital‐based (both referral and local) Past history of TB: Participants on anti‐TB treatment: Number of specimens evaluated: 610 Laboratory level: central in South Africa Country: South Africa, Vietnam, Indonesia World Bank Income Classification: middle High TB burden: South Africa yes; Vietnam yes; Indonesia yes High TB/HIV burden: South Africa yes; Vietnam no; Indonesia yes High MDR‐TB burden: South Africa yes; Vietnam yes; Indonesia yes
Index tests	Xpert MTB/RIF WHO SOP or manufacturer's protocol followed: no (as performed in Nhu 2014)
Target condition and reference standard(s)	TB meningitis CRS: clinical TB meningitis, diagnosis (definite, probable and possible TB meningitis); MGIT (MODS Indonesia) Speciation yes Decontamination: no
Flow and timing
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (Xpert MTB/RIF)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 2: Index Test (Xpert Ultra)
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
For rifampicin resistance testing, were the reference standard results interpreted without knowledge of the results of the index test?
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk