Applying a consensus case definition to patients with confirmed tuberculous meningitis

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. Electronic address: .
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases (Impact Factor: 1.86). 06/2012; 16(10):e758-9. DOI: 10.1016/j.ijid.2012.04.013
Source: PubMed

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    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.
    No preview · Article · Oct 2013 · Current Infectious Disease Reports
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    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.
    Full-text · Article · Oct 2014 · The Lancet Infectious Diseases
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    ABSTRACT: Background: Tuberculous meningitis (TBM) is the most lethal form of Mycobacterium tuberculosis infection, which has a high rate of neurological complications and sequelae. Objectives: Our study offers a real-world infectious disease clinic perspective, being thus representative for the clinical environment of developing countries. Methods: We performed a retrospective analysis of the 127 adult and 77 pediatric cases diagnosed with TBM in the Infectious Disease Hospital of the School of Medicine of Iasi, Romania between 2004-2013. Results: Definite diagnosis of TBM was established in 31% of children but in only 20% of adults (p = 0.043). A contact with an individual with pulmonary tuberculosis was documented in 30% of children vs. 13% of adults (p = 0.0007). Coma occurred in 19% of patients (similar in children and adults); other consciousness abnormalities were seen in 27% of children and in 72% of adults (p = 0.000001). Cranial nerve palsies occurred prior to therapy in 9% of cases (12% vs 7% of children and adults, respectively, p>0.05), and developed 2-7 days after treatment initiation in 10% (12 vs 9%). CSF cultures were positive for M. tuberculosis in 24% of patients (31% vs. 20%, p>0.05). Overall mortality was 7.35%, similar for children and adults. Yet, permanent neurological sequelae, which were seen in 23% of patients occurred significantly more frequent in children vs. adults (36% vs. 14%, respectively, p = 0.0121). In conclusion, our retrospective analysis on a significant number of cases of TBM identified striking differences between children and adults: while children were in an earlier stage at the admission, they associated a higher frequency of neurological sequelae and miliary pattern, and they were more likely to have normal CSF protein levels and positive cultures of CSF.
    Full-text · Article · Jul 2015 · PLoS ONE