Tuberculous meningitis diagnosis and outcomes during the Xpert MTB/Rif era: a 6.5-year cohort study in Uganda
Year: 2018
Type: article
Abstract: Background: Tuberculous meningitis (TBM), a leading cause of meningitis in sub-Saharan Africa, is notoriously difficult to diagnose. In our Ugandan setting TB diagnostics have evolved rapidly in recent years, with introduction of Xpert MTB/Rif (Xpert) in 2011 and culture in 2013. We aim to describe the impact of improved TBM diagnostics at two Ugandan hospitals between 2010 and 2017. Methods: Adults presenting with meningitis (headache and objective meningism) were assessed for eligibility for enrolment in two consecutive trials investigating cryptococcal meningitis. 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 cryptococcal antigen (crAg). In a post-hoc analysis of three prospective cohorts, we compare rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 predominantly HIV-infected adults underwent lumbar puncture, of which 33% (558/1672) had negative CSF crAg and 12% (195/1672) were treated for TBM. 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). Adjusting for definite TBM and antiretroviral therapy, and using imputed data, 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: Since 2010, as TBM diagnostics have evolved, microbiologically-confirmed TBM diagnoses have increased significantly. There has been a non-significant decline in TBM in-hospital mortality but due to multiple possible confounding factors it is not possible to conclude what has driven this decline in mortality.
Source: Wellcome Open Research
Institutions: University of Cape Town, London School of Hygiene & Tropical Medicine, Infectious Diseases Institute, National Hospital for Neurology and Neurosurgery, University College London, University of Minnesota, University of Kansas, University of Utah, Mbarara University of Science and Technology, MRC/UVRI & LSHTM Uganda Research Unit, Makerere University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,128
Funders: Wellcome Trust, Government of the United Kingdom, National Institute for Health and Care Research, New Partnership for Africa's Development, African Academy of Sciences, Medical Research Council, Alliance for Accelerating Excellence in Science in Africa, Fogarty International Center, National Institute of Neurological Disorders and Stroke
Awards: Makerere University UVRI Centre of Excellence for Infection & Immunity Research and Training (MUII-plus), G3899637757, G7279930290, G7853697249, Improving diagnosis and treatment of TB meningitis, G857320834, Improving diagnosis and treatment of TB meningitis, Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related Meningitis
OpenAlex ID: W2805348151