TY - JOUR
T1 - Tuberculous meningitis
AU - on behalf of the Tuberculous Meningitis International Research Consortium
AU - Wilkinson, Robert J.
AU - Rohlwink, Ursula
AU - Misra, Usha Kant
AU - Van Crevel, Reinout
AU - Mai, Nguyen Thi Hoang
AU - Dooley, Kelly E.
AU - Caws, Maxine
AU - Figaji, Anthony
AU - Savic, Rada
AU - Solomons, Regan
AU - Thwaites, Guy E.
AU - Aarnoutse, Rob
AU - Van Laarhoven, Aarjan
AU - Dian, Sofiati
AU - Bahr, Nathan C.
AU - Boulware, David R.
AU - Cronan, Mark R.
AU - Tobin, David
AU - Dunstan, Sarah
AU - Feng, Guo Dong
AU - Shi, Xiaodan
AU - Wang, Ting
AU - Marais, Suzaan
AU - McIlleron, Helen
AU - Meintjes, Graeme
AU - Rizal, Ahmad
AU - Ruslami, Rovina
AU - Garg, Ravindra K.
AU - Gupta, Mudit
AU - Gupta, Rakesh K.
AU - Gupta, Sneha
AU - Heemskerk, Anna D.
AU - Nguyên, Thuong Thuy Thuong
AU - Nguyên, Mai Thi Hoàng
AU - Srinivasan, Vijay
AU - Trân, Trâm Thi Bích
AU - Vân Trân, Thinh Thi
AU - Trân, Anh Thi Ngoc
AU - Vo, Trang Hông Yêng
AU - Wolbers, Marcel
AU - Kalita, Jayantee
AU - Misra, Usha K.
AU - Lai, Rachel
AU - Marais, Ben J.
AU - Trinh, Mai Quýnh
AU - Nguyên, Bâng Dúc
AU - Nguyên, Yên Bích
AU - Patel, Vinod
AU - Pouplin, Thomas
AU - Ramakrishnan, Lalita
N1 - Funding Information:
Institute of Medical Sciences, New Delhi, India); Douwe H. Visser (VU University Medical Center, Amsterdam, The Netherlands); Robert J. Wilkinson (Imperial College and The Francis Crick Institute, London, UK and University of Cape Town, South Africa). R.J.W. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC00110218), the UK Medical Research Council (FC00110218), and the Wellcome Trust (FC00110218). He also receives support from the Wellcome Trust (104803, 203135) and the National Research Foundation Of South Africa (96841). G.T. is supported by the Wellcome Trust through a Major Overseas Programme grant (106680/Z/14/Z) and an Investigator Award (110179/Z/15/Z).
Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies-including corticosteroids, aspirin and thalidomide-has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM.
AB - Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies-including corticosteroids, aspirin and thalidomide-has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM.
UR - http://www.scopus.com/inward/record.url?scp=85032585660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032585660&partnerID=8YFLogxK
U2 - 10.1038/nrneurol.2017.120
DO - 10.1038/nrneurol.2017.120
M3 - Review article
C2 - 28884751
AN - SCOPUS:85032585660
SN - 1759-4758
VL - 13
SP - 581
EP - 598
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 10
ER -