National Institute of Infectious Diseases "Prof. Dr. Matei Bals", Str. Calistrat Grozovici, No.1, Sect. 2, Bucharest 021105, Romania; "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. Electronic address: .
[Show abstract][Hide abstract] ABSTRACT: Background
Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: Mycobacterium tuberculosis is one of the most prevalent human infections. Although the largest share of the burden of disease is in Africa and Asia, tuberculosis has a global footprint due to travel and migration. Resource constraints in many low- and middle-income countries are hampering efforts to control new infections and to prevent drug resistance. Infection of the central nervous system by Mycobacterium tuberculosis includes meningitis, tuberculoma, and abscess and carries a high morbidity and mortality. High clinical suspicion, combined with cerebrospinal fluid analysis and brain imaging studies, can improve the diagnostic certainty. The recent scale-up of nucleic acid amplification technology may allow earlier diagnosis of tuberculous meningitis in many regions of the world. Treatment of tuberculous infection of the central nervous system is usually empirical and follows conventional regimens for pulmonary tuberculosis. The optimal treatment regimen is still being elucidated and has been the subject of recent clinical trials.
Current Infectious Disease Reports 10/2013;
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