Abstract
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.
Highlights
Tuberculous meningitis (TBM) is the second most common cause of adult meningitis in sub-Saharan Africa[1,2], accounting for one to five percent of the 10.4 million tuberculosis (TB) cases reported worldwide in 20163
To clarify who was eligible to be included in the diagnostic analysis and TBM cohort (n=195) we have added to the methods that “any patient from the 1672 patients screened who received testing for TBM (AFB smear, Xpert or culture) was eligible to be included in the diagnostic analysis and any patient who was treated for TBM was eligible to be included in the TBM cohort”
Participant characteristics Over the study period, 1672 patients with meningitis symptoms were assessed and underwent lumbar puncture: 1058 (63%) had a positive cerebrospinal fluid (CSF) cryptococcal antigen test, 558 (33%) had negative CSF cryptococcal antigen test
Summary
Tuberculous meningitis (TBM) is the second most common cause of adult meningitis in sub-Saharan Africa[1,2], accounting for one to five percent of the 10.4 million tuberculosis (TB) cases reported worldwide in 20163. Insidious symptom onset in persons with TBM leads to delay in seeking care and increasing disease severity at presentation correlates with higher mortality[7]. Tuberculous meningitis (TBM), a leading cause of meningitis in sub-Saharan Africa, is notoriously difficult to diagnose. Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume CSF (2013-2017) for all meningitis suspects with a negative CSF version 2 (revision)
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