Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis

Chiang, Silvia S.; Khan, Faiz Ahmad; Milstein, M; Tolman, Arielle W.; Benedetti, Andrea; Starke, Jeffrey R.; Becerra, Mercedes C.

doi:10.1016/s1473-3099(14)70852-7

Cited by 256 publications

(224 citation statements)

References 35 publications

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“…Despite extensive research efforts, the diagnosis and treatment of TBM is often delayed because of its insidious onset (Wilkinson et al, 2017). Consequently, half of the patients are diagnosed in the most advanced stage of disease, resulting in a high mortality rate of nearly 20% and neurological sequelae in more than half of the survivors (Chiang et al, 2014). These poor odds of (full) recovery for TBM patients can be mostly attributed to the severe neuro‐inflammation at the base of the brain, on‐going neural ischaemia, and vasculitis (Donald & Van Toorn, 2016).…”

Section: Introductionmentioning

confidence: 99%

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Leeuwen

Boot

Kuijl

et al. 2018

Cellular Microbiology

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Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialised barriers protecting the brain. How M. tuberculosis crosses the blood–brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development, mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages. After the formation of a functionally intact BBB, the infiltration of brain tissue by infected macrophages is delayed, but not blocked, suggesting that crossing the BBB via phagocytic cells is one of the mechanisms used by mycobacteria to invade the CNS. Interestingly, depletion of phagocytic cells did not prevent M. marinum from infecting the brain tissue, indicating that free mycobacteria can independently cause brain infection. Detailed analysis showed that mycobacteria are able to cause vasculitis by extracellular outgrowth in the smaller blood vessels and by infecting endothelial cells. Importantly, we could show that this second mechanism is an active process that depends on an intact ESX‐1 secretion system, which extends the role of ESX‐1 secretion beyond the macrophage infection cycle.

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Section: Introductionmentioning

confidence: 99%

Mycobacteria employ two different mechanisms to cross the blood-brain barrier

Leeuwen

Boot

Kuijl

et al. 2018

Cellular Microbiology

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“…Risk factors for meningitis include: skipping vaccinations, age (most cases of viral meningitis occur in children younger than five years old and bacterial meningitis commonly affects people under 20), living in a community setting (college students living in dormitories, personnel on military bas-es, and children in boarding schools and child care facilities are at increased risk of meningococcal meningitis), and factors that may compromise patients' immune system including; AIDS, use of immunosuppressant drugs, and removal of the spleen (3-6). There are many reports about the epidemiology of meningitis and according to the community under study, age of cases and other risk factors, agents and clinical outcome are different (8)(9)(10)(11)(12)(13)(14)(15)(16)). …”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Meningitis Studied at a University Hospital in Zahedan, South-Eastern Iran

et al. 2015

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Background:Meningitis is an inflammation of the membranes, which surround the brain and spinal cord. Early treatment of bacterial meningitis can prevent serious complications. In the last two decades, three vaccines have been developed against the three main bacterial species implicated in meningitis of children in western countries and vaccine-preventable invasive bacterial meningitis has decreased substantially in the past few years. However, none of the developed vaccines are part of our childhood immunization schedule. Objectives: This study aimed to search the epidemiology of meningitis in Zahedan. Patients and Methods:In this cross-sectional survey, we studied all patients with meningitis for ten years, from May 2004 to May 2014, who had been referred to our hospital. The patients were evaluated according to their sex, age, clinical features, risk factors, pathogenic microorganisms, form of infection (acute or chronic) and clinical outcome. Results: Among the 53 patients with meningitis (47% females; 53% males with mean age 36 years) 47 cases (83%) had acute meningitis and six cases (17%) had chronic meningitis (four cases of tuberculosis and two cases of brucellosis). From the 47 cases with acute meningitis, only one case had a positive cerebrospinal fluid (CSF) culture for meningococci and 46 patients had negative CSF culture. The most common clinical symptoms was fever and headache (90%) and the least was seizure (9%). Mortality rate was 7.5% (4 cases). There were no significant risk factors except for two patients with acute meningitis and two cases with chronic meningitis. Conclusions: According to negative CSF cultures in acute meningitis, CSF culture using the BACTEC automated system and specific viral tests is recommended for detection of the etiological agents of viral and bacterial meningitis, particularly in the Iranian population where patients use antibiotics without prescription.

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“…Rohlwink et al 3 report a high yield (53%) from CSF cultures and ascertain the diagnosis of tuberculous meningitis in a substantially higher proportion than results compiled in a recent meta-analysis. 5 Their study confirms the improvement in laboratory diagnosis procedures and emphasizes the contribution of drug susceptibility testing, as multi-drug resistance might have contributed to the mortality at least in some children. Negative bacteriological results with the currently available techniques should prompt to consider other diagnoses.…”

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confidence: 52%