Silvia S Chiang1, Faiz Ahmad Khan2, Meredith B Milstein2, Arielle W Tolman2, Andrea Benedetti3, Jeffrey R Starke4, Mercedes C Becerra5. 1. Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: schiang@alumni.stanford.edu. 2. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA. 3. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada; Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada. 4. Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. 5. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA; Partners In Health, Boston, MA, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA.
Abstract
BACKGROUND: Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. METHODS: We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. FINDINGS: 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2). INTERPRETATION: Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. FUNDING: None.
BACKGROUND:Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. METHODS: We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. FINDINGS: 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2). INTERPRETATION: Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. FUNDING: None.
Authors: Elizabeth W Tucker; Beatriz Guglieri-Lopez; Alvaro A Ordonez; Brittaney Ritchie; Mariah H Klunk; Richa Sharma; Yong S Chang; Julian Sanchez-Bautista; Sarah Frey; Martin A Lodge; Steven P Rowe; Daniel P Holt; Jogarao V S Gobburu; Charles A Peloquin; William B Mathews; Robert F Dannals; Carlos A Pardo; Sujatha Kannan; Vijay D Ivaturi; Sanjay K Jain Journal: Sci Transl Med Date: 2018-12-05 Impact factor: 17.956
Authors: Helen E Jenkins; Courtney M Yuen; Carly A Rodriguez; Ruvandhi R Nathavitharana; Megan M McLaughlin; Peter Donald; Ben J Marais; Mercedes C Becerra Journal: Lancet Infect Dis Date: 2016-12-08 Impact factor: 25.071