Tuberculous meningitis: a uniform case definition for use in clinical research

Marais, Suzaan; Thwaites, Guy; Schoeman, Johan; Török, M. Estée; Misra, U. K.; Prasad, Kameshwar; Donald, Peter R.; Wilkinson, Robert J.; Marais, Ben J.

doi:10.1016/s1473-3099(10)70138-9

Cited by 721 publications

(801 citation statements)

References 70 publications

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“…Consensus uniform case definitions were used to categorise patients as definite, probable, possible or not TBM 11 . In addition to the consensus case definitions, clinical TBM was defined as subjects without a positive microbiologic result, but who were treated empirically for TBM treatment due to high clinical suspicion.…”

Section: Methodsmentioning

confidence: 99%

“…Sensitivity of Xpert MTB/Rif was evaluated against a composite reference standard (any positive CSF test - AFB smear, Xpert or culture i.e. definite TBM according to the uniform case definition) 11 . A separate analysis was conducted against the uniform case definition of probable or definite TBM 11 .…”

Section: Methodsmentioning

confidence: 99%

“…definite TBM according to the uniform case definition) 11 . A separate analysis was conducted against the uniform case definition of probable or definite TBM 11 . Concordance between Xpert MTB/Rif and culture was evaluated with a kappa statistic and McNemar’s test.…”

Section: Methodsmentioning

confidence: 99%

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Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Cresswell¹,

Bangdiwala²,

Bahr³

et al. 2018

Wellcome Open Res

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Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P<0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Cresswell¹,

Bangdiwala²,

Bahr³

et al. 2018

Wellcome Open Res

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“…First, we used the uniform clinical case definition as described by Marais and colleagues. 10 We categorised participants as definite, probable, possible, and not tuberculous meningitis. We defined definite tuberculous meningitis in accordance with the consensus definition as any CSF test positivity by microscopy, culture, or commercialised PCR (including Xpert or Xpert Ultra).…”

Section: Implications Of All the Available Evidencementioning

confidence: 99%

“…9 Sensitivity compared with consensus clinical case definition was only 36%. 9,10 The second large cohort study, in Vietnam, measured Xpert against the same clinical case definition and found 59% sensitivity generally using 2 mL or less of centrifuged CSF. 11,12 A third Ugandan study reported 28% sensitivity with 2 mL of uncentrifuged CSF and 72% sensitivity when centrifuging a median volume of 6 mL (IQR 4-10) with Xpert.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: A prospective cohort study

2018

Indian Journal of Tuberculosis

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Safety and Efficacy of Fludrocortisone in the Treatment of Cerebral Salt Wasting in Patients With Tuberculous Meningitis

2018

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IMPORTANCE Tuberculous meningitis is associated with high frequency of cerebral salt wasting. There is a paucity of objective information regarding the best method of treatment of this condition.OBJECTIVE To evaluate the efficacy and safety of fludrocortisone in the treatment of cerebral salt wasting in patients with tuberculous meningitis. DESIGN, SETTING, AND PARTICIPANTSThis is a single-center, open-label, randomized clinical trial conducted from October 2015 to April 2017 in India. Patients were randomized in a 1:1 ratio to arms receiving saline only or saline plus fludrocortisone, in addition to a standard treatment of 4 antitubercular drugs, prednisolone, and aspirin. The 2 arms were matched for demographic, clinical, and magnetic resonance imaging findings. The patients were followed up for at least 6 months.INTERVENTIONS Patients were randomized to a 0.9% solution of intravenous saline with 5 to 12 g per day of oral salt supplementation, with or without the addition of 0.1 to 0.4 mg of fludrocortisone per day. MAIN OUTCOMES AND MEASURESThe primary end point was the time needed to correct serum sodium levels; secondary end points were in-hospital deaths, disability at 3 months, disability at 6 months, occurence of stroke, and serious adverse reactions.RESULTS Ninety-three patients with suspected tuberculous meningitis were recruited; 12 did not meet the inclusion criteria, including 4 with alternate diagnoses. A total of 37 patients with cerebral salt wasting were eligible for the study. One refused to participate, and therefore 36 patients were included, with 18 randomized to each group. The median (range) age was 30 (20-46) years, and 19 were male (52.8%). Those receiving fludrocortisone regained normal serum sodium levels after 4 days, significantly earlier than those receiving saline only (15 days; P = .004). In an intention-to-treat analysis, hospital mortality, disability at 3 months, and disability at 6 months did not differ significantly, but fewer infarcts occurred in the deep border zone in the group receiving fludrocortisone (1 of 18 [6%]) vs those in the control arm (6 of 18 [33%]; P = .04). Fludrocortisone was associated with severe hypokalemia and hypertension in 2 patients each, and pulmonary edema occurred in 1 patient. These adverse reactions necessitated discontinuation of fludrocortisone in 2 patients.CONCLUSIONS AND RELEVANCE Fludrocortisone results in earlier normalization of serum sodium levels, but did not affect outcomes at 6 months. Fludrocortisone had to be withdrawn in 2 patients because of severe adverse effects. This study provides class II evidence on the role of fludrocortisone in treatment of hyponatremia associated with cerebral salt wasting in patients with tuberculous meningitis.TRIAL REGISTRATION Clinical Trials Registry of India (ctri.nic.in) Identifier: CTRI/2017/10 /010255

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Tuberculous meningitis: a uniform case definition for use in clinical research

Cited by 721 publications

References 70 publications

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: A prospective cohort study

Safety and Efficacy of Fludrocortisone in the Treatment of Cerebral Salt Wasting in Patients With Tuberculous Meningitis

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