Skip to main content

Advertisement

Log in

Tuberculosis Meningitis

  • Central Nervous System Infections (K Bloch, Section Editor)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

As the most severe form of tuberculosis (TB), TB meningitis disproportionately affects developing countries and results in significant morbidity and mortality. In this report, we review recent updates in the epidemiology, diagnosis, and management of TB meningitis.

Recent Findings

Young children and people living with HIV continue to be at highest risk for TB meningitis. Early diagnosis remains challenging, especially since conventional diagnostic tests have sub-optimal sensitivity and specificity. Recently, nucleic acid amplification testing emerged as the preferred diagnostic modality due to its rapid turnaround time and high specificity.

Summary

Several recent studies have assessed the optimal treatment for TB meningitis. While the benefit of treatment intensification, by increasing rifampin dosing or adding a fluoroquinolone, is unclear, a growing body of evidence suggests that steroids confer a survival advantage, particularly in patients with mild disease. Additionally, TB meningitis management is further complicated by high rates of HIV co-infection. Recent data suggest that unlike other forms of TB, early initiation of antiretroviral therapy in patients with TB meningitis is associated with higher rates of adverse reactions, without improved survival.

TB meningitis continues to be a significant problem worldwide. Despite recent advances, more studies are warranted to improve early disease detection and optimize therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Van TT, Farrar J. Tuberculous meningitis. J Epidemiol Community Health. 2014;68(3):195–6. https://doi.org/10.1136/jech-2013-202525.

    Article  PubMed  Google Scholar 

  2. Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev. 2008;21(2):243–261, table of contents. https://doi.org/10.1128/CMR.00042-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol. 2013;12(10):999–1010. https://doi.org/10.1016/S1474-4422(13)70168-6.

    Article  CAS  PubMed  Google Scholar 

  4. Torok ME. Tuberculous meningitis: advances in diagnosis and treatment. Br Med Bull. 2015;113(1):117–31. https://doi.org/10.1093/bmb/ldv003.

    Article  CAS  PubMed  Google Scholar 

  5. World Health Organization. Global tuberculosis report 2016. 2016.

  6. Murthy JM. Tuberculous meningitis: the challenges. Neurol India. 2010;58(5):716–22. https://doi.org/10.4103/0028-3886.72178.

    Article  CAS  PubMed  Google Scholar 

  7. van Well GT, Paes BF, Terwee CB, Springer P, Roord JJ, Donald PR, et al. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa. Pediatrics. 2009;123(1):e1–8.

    Article  PubMed  Google Scholar 

  8. Berenguer J, Moreno S, Laguna F, Vicente T, Adrados M, Ortega A, et al. Tuberculous meningitis in patients infected with the human immunodeficiency virus. N Engl J Med. 1992;326(10):668–72. https://doi.org/10.1056/NEJM199203053261004.

    Article  CAS  PubMed  Google Scholar 

  9. Kingkaew N, Sangtong B, Amnuaiphon W, Jongpaibulpatana J, Mankatittham W, Akksilp S, et al. HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death. Int J Infect Dis. 2009;13(6):722–9. https://doi.org/10.1016/j.ijid.2008.11.013.

    Article  CAS  PubMed  Google Scholar 

  10. Leeds IL, Magee MJ, Kurbatova EV, del Rio C, Blumberg HM, Leonard MK, et al. Site of extrapulmonary tuberculosis is associated with HIV infection. Clin Infect Dis. 2012;55(1):75–81.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Schoeman JF, Donald PR. Chapter 117—tuberculous meningitis. In: Olivier Dulac ML, Harvey BS, editors. Handbook of clinical neurology. Elsevier; 2013. p. 1135–8.

    Google Scholar 

  12. Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351(17):1741–51. https://doi.org/10.1056/NEJMoa040573.

    Article  CAS  PubMed  Google Scholar 

  13. Sinha MK, Garg RK, Anuradha H, Agarwal A, Singh MK, Verma R, et al. Vision impairment in tuberculous meningitis: predictors and prognosis. J Neurol Sci. 2010;290(1–2):27–32. https://doi.org/10.1016/j.jns.2009.12.012.

    Article  PubMed  Google Scholar 

  14. Mai NT, Thwaites GE. Recent advances in the diagnosis and management of tuberculous meningitis. Curr Opin Infect Dis. 2017;30(1):123–8. https://doi.org/10.1097/QCO.0000000000000331.

    CAS  PubMed  Google Scholar 

  15. Schmit KM, Wansaula Z, Pratt R, Price SF, Langer AJ. Tuberculosis—United States, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(11):289–94. https://doi.org/10.15585/mmwr.mm6611a2.

    Article  PubMed  Google Scholar 

  16. Centers for Disease Control and Prevention (CDC). Reported tuberculosis in the United States, 2015. Atlanta: US Department of Health and Human Services, CDC; 2016.

    Google Scholar 

  17. Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006. Clin Infect Dis. 2009;49(9):1350–7. https://doi.org/10.1086/605559.

    Article  PubMed  Google Scholar 

  18. Pehlivanoglu F, Yasar KK, Sengoz G. Tuberculous meningitis in adults: a review of 160 cases. ScientificWorldJournal. 2012;2012:169028. https://doi.org/10.1100/2012/169028.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sharma P, Garg RK, Verma R, Singh MK, Shukla R. Incidence, predictors and prognostic value of cranial nerve involvement in patients with tuberculous meningitis: a retrospective evaluation. Eur J Intern Med. 2011;22(3):289–95. https://doi.org/10.1016/j.ejim.2011.01.007.

    Article  PubMed  Google Scholar 

  20. Youssef FG, Afifi SA, Azab AM, Wasfy MM, Abdel-Aziz KM, Parker TM, et al. Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters. Diagn Microbiol Infect Dis. 2006;55(4):275–8.

    Article  CAS  PubMed  Google Scholar 

  21. Hristea A, Olaru ID, Baicus C, Moroti R, Arama V, Ion M. Clinical prediction rule for differentiating tuberculous from viral meningitis. Int J Tuberc Lung Dis. 2012;16(6):793–8. https://doi.org/10.5588/ijtld.11.0687.

    CAS  PubMed  Google Scholar 

  22. Vibha D, Bhatia R, Prasad K, Srivastava MP, Tripathi M, Kumar G, et al. Validation of diagnostic algorithm to differentiate between tuberculous meningitis and acute bacterial meningitis. Clin Neurol Neurosurg. 2012;114(6):639–44.

    Article  PubMed  Google Scholar 

  23. Zhang YL, Lin S, Shao LY, Zhang WH, Weng XH. Validation of Thwaites’ diagnostic scoring system for the differential diagnosis of tuberculous meningitis and bacterial meningitis. Jpn J Infect Dis. 2014;67(6):428–31.

    Article  PubMed  Google Scholar 

  24. Cohen DB, Zijlstra EE, Mukaka M, Reiss M, Kamphambale S, Scholing M, et al. Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Tropical Med Int Health. 2010;15(8):910–7. https://doi.org/10.1111/j.1365-3156.2010.02565.x.

    Article  Google Scholar 

  25. Patel VB, Singh R, Connolly C, Kasprowicz V, Zumla A, Ndungu T, et al. Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. PLoS One. 2010;5(12):e15664. https://doi.org/10.1371/journal.pone.0015664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jackson A, van der Horst C. New insights in the prevention, diagnosis, and treatment of cryptococcal meningitis. Curr HIV/AIDS Rep. 2012;9(3):267–77. https://doi.org/10.1007/s11904-012-0127-7.

    Article  PubMed  Google Scholar 

  27. Erdem H, Ozturk-Engin D, Elaldi N, Gulsun S, Sengoz G, Crisan A, et al. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect. 2014;20(10):O600–8. https://doi.org/10.1111/1469-0691.12478.

    Article  CAS  PubMed  Google Scholar 

  28. Thwaites GE, Chau TT, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol. 2004;42(1):378–9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chen P, Shi M, Feng GD, Liu JY, Wang BJ, Shi XD, et al. A highly efficient Ziehl-Neelsen stain: identifying de novo intracellular Mycobacterium tuberculosis and improving detection of extracellular M. tuberculosis in cerebrospinal fluid. J Clin Microbiol. 2012;50(4):1166–70. https://doi.org/10.1128/JCM.05756-11.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Feng GD, Shi M, Ma L, Chen P, Wang BJ, Zhang M, et al. Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis. Am J Respir Crit Care Med. 2014;189(4):475–81. https://doi.org/10.1164/rccm.201309-1686OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Caws M, Dang TM, Torok E, Campbell J, Do DA, Tran TH, et al. Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis. PLoS One. 2007;2(11):e1173. https://doi.org/10.1371/journal.pone.0001173.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tuon FF, Higashino HR, Lopes MI, Litvoc MN, Atomiya AN, Antonangelo L, et al. Adenosine deaminase and tuberculous meningitis—a systematic review with meta-analysis. Scand J Infect Dis. 2010;42(3):198–207. https://doi.org/10.3109/00365540903428158.

    Article  CAS  PubMed  Google Scholar 

  33. Corral I, Quereda C, Navas E, Martin-Davila P, Perez-Elias MJ, Casado JL, et al. Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis. Eur J Clin Microbiol Infect Dis. 2004;23(6):471–6. https://doi.org/10.1007/s10096-004-1110-z.

    Article  CAS  PubMed  Google Scholar 

  34. Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford JM Jr. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2003;3(10):633–43.

    Article  CAS  PubMed  Google Scholar 

  35. Takahashi T, Nakayama T. Novel technique of quantitative nested real-time PCR assay for Mycobacterium tuberculosis DNA. J Clin Microbiol. 2006;44(3):1029–39. https://doi.org/10.1128/JCM.44.3.1029-1039.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bhigjee AI, Padayachee R, Paruk H, Hallwirth-Pillay KD, Marais S, Connoly C. Diagnosis of tuberculous meningitis: clinical and laboratory parameters. Int J Infect Dis. 2007;11(4):348–54. https://doi.org/10.1016/j.ijid.2006.07.007.

    Article  CAS  PubMed  Google Scholar 

  37. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005–15. https://doi.org/10.1056/NEJMoa0907847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 2011;6(9):1067–82.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chang K, Lu W, Wang J, Zhang K, Jia S, Li F, et al. Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis. J Inf Secur. 2012;64(6):580–8. https://doi.org/10.1016/j.jinf.2012.02.012.

    Google Scholar 

  40. Patel VB, Theron G, Lenders L, Matinyena B, Connolly C, Singh R, et al. Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. PLoS Med. 2013;10(10):e1001536. https://doi.org/10.1371/journal.pmed.1001536.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Nhu NT, Heemskerk D, do DA T, Chau TT, Mai NT, Nghia HD, et al. Evaluation of GeneXpert MTB/RIF for diagnosis of tuberculous meningitis. J Clin Microbiol. 2014;52(1):226–33. https://doi.org/10.1128/JCM.01834-13.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2014;44(2):435–46. https://doi.org/10.1183/09031936.00007814.

    Article  PubMed  Google Scholar 

  43. World Health Organization. Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children: policy update. 2013.

  44. Bahr NC, Tugume L, Rajasingham R, Kiggundu R, Williams DA, Morawski B, et al. Improved diagnostic sensitivity for tuberculous meningitis with Xpert((R)) MTB/RIF of centrifuged CSF. Int J Tuberc Lung Dis. 2015;19(10):1209–15. https://doi.org/10.5588/ijtld.15.0253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bahr NC, Marais S, Caws M, van Crevel R, Wilkinson RJ, Tyagi JS, et al. GeneXpert MTB/RIF to diagnose tuberculous meningitis: perhaps the first test but not the last. Clin Infect Dis. 2016;62(9):1133–5.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Cepheid. 2017 launch of new TB test Ultra backed by WHO recommendation. http://www.cepheid.com/us/about-us/news-events/press-releases/216-2017-launch-of-new-tb-test-ultra-backed-by-who-recommendation. Accessed 08/10/2017.

  47. WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTF/RIF Ultra compared to Xpert MTB/RIF. Geneva: World Health Organization; 2017 (WHO/HTM/TB/2017.04). Licence: CC BY-NCSA 3.0 IGO.

  48. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection-United States, 2010. MMWR Recomm Rep. 2010;59(RR-5):1–25.

    PubMed  Google Scholar 

  49. Patel VB, Singh R, Connolly C, Coovadia Y, Peer AK, Parag P, et al. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population. Am J Respir Crit Care Med. 2010;182(4):569–77. https://doi.org/10.1164/rccm.200912-1931OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kim SH, Cho OH, Park SJ, Lee EM, Kim MN, Lee SO, et al. Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells. Clin Infect Dis. 2010;50(10):1349–58. https://doi.org/10.1086/652142.

    Article  CAS  PubMed  Google Scholar 

  51. Yu J, Wang ZJ, Chen LH, Li HH. Diagnostic accuracy of interferon-gamma release assays for tuberculous meningitis: a meta-analysis. Int J Tuberc Lung Dis. 2016;20(4):494–9. https://doi.org/10.5588/ijtld.15.0600.

    Article  CAS  PubMed  Google Scholar 

  52. Torres C, Riascos R, Figueroa R, Gupta RK. Central nervous system tuberculosis. Top Magn Reson Imaging. 2014;23(3):173–89. https://doi.org/10.1097/RMR.0000000000000023.

    Article  PubMed  Google Scholar 

  53. Pienaar M, Andronikou S, van Toorn R. MRI to demonstrate diagnostic features and complications of TBM not seen with CT. Childs Nerv Syst. 2009;25(8):941–7. https://doi.org/10.1007/s00381-008-0785-3.

    Article  PubMed  Google Scholar 

  54. Botha H, Ackerman C, Candy S, Carr JA, Griffith-Richards S, Bateman KJ. Reliability and diagnostic performance of CT imaging criteria in the diagnosis of tuberculous meningitis. PLoS One. 2012;7(6):e38982. https://doi.org/10.1371/journal.pone.0038982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kalita J, Prasad S, Maurya PK, Kumar S, Misra UKMR. Angiography in tuberculous meningitis. Acta Radiol. 2012;53(3):324–9. https://doi.org/10.1258/ar.2012.110712.

    Article  PubMed  Google Scholar 

  56. Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147–e95. https://doi.org/10.1093/cid/ciw376.

    Article  PubMed  Google Scholar 

  57. World Health Organization, Stop TB Initiative. Treatment of tuberculosis: guidelines. Geneva: World Health Organization; 2010.

    Google Scholar 

  58. Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J, et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Inf Secur. 2009;59(3):167–87. https://doi.org/10.1016/j.jinf.2009.06.011.

    Google Scholar 

  59. World Health Organization. Guidelines for the treatment of drug-susceptible tuberculosis and patient care, 2017 update. 2017.

  60. Nelson CA, Zunt JR. Tuberculosis of the central nervous system in immunocompromised patients: HIV infection and solid organ transplant recipients. Clin Infect Dis. 2011;53(9):915–26. https://doi.org/10.1093/cid/cir508.

    Article  PubMed  PubMed Central  Google Scholar 

  61. • Heemskerk AD, Bang ND, Mai NT, Chau TT, Phu NH, Loc PP, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374(2):124–34. https://doi.org/10.1056/NEJMoa1507062. This randomized clinical trial conducted at two centers in Vietnam evaluated whether TB meningitis survival rates improved with treatment intensification through increased rifampin dosing and adding levofloxacin. During 9 months of follow-up and compared to patients treated with standard therapy, treatment intensification did not confer a significant survival benefit. Moreover, intensified treatment was associated with increased, albeit not statistically significant, rates of adverse events.

    Article  CAS  PubMed  Google Scholar 

  62. Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, van der Ven AJ, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013;13(1):27–35. https://doi.org/10.1016/S1473-3099(12)70264-5.

    Article  PubMed  Google Scholar 

  63. Thwaites GE, Bhavnani SM, Chau TT, Hammel JP, Torok ME, Van Wart SA, et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother. 2011;55(7):3244–53. https://doi.org/10.1128/AAC.00064-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Torok ME, Aljayyoussi G, Waterhouse D, Chau T, Mai N, Phu NH, et al. Suboptimal exposure to anti-TB drugs in a TBM/HIV+ population is not related to anti-retroviral therapy. Clin Pharmacol Ther. 2017; https://doi.org/10.1002/cpt.646.

  65. van Loenhout-Rooyackers JH, Keyser A, Laheij RJ, Verbeek AL, van der Meer JW. Tuberculous meningitis: is a 6-month treatment regimen sufficient? Int J Tuberc Lung Dis. 2001;5(11):1028–35.

    PubMed  Google Scholar 

  66. Jullien S, Ryan H, Modi M, Bhatia R. Six months therapy for tuberculous meningitis. Cochrane Database Syst Rev. 2016;9:CD012091. https://doi.org/10.1002/14651858.CD012091.pub2.

    PubMed  Google Scholar 

  67. Garg RK, Jain A, Malhotra HS, Agrawal A, Garg R. Drug-resistant tuberculous meningitis. Expert Rev Anti-Infect Ther. 2013;11(6):605–21. https://doi.org/10.1586/eri.13.39.

    Article  CAS  PubMed  Google Scholar 

  68. Vinnard C, Winston CA, Wileyto EP, Macgregor RR, Bisson GP. Isoniazid resistance and death in patients with tuberculous meningitis: retrospective cohort study. BMJ. 2010;341:c4451. https://doi.org/10.1136/bmj.c4451.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Nagarathna S, Rafi W, Veenakumari HB, Mani R, Satishchandra P, Chandramuki A. Drug susceptibility profiling of tuberculous meningitis. Int J Tuberc Lung Dis. 2008;12(1):105–7.

    CAS  PubMed  Google Scholar 

  70. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva: World Health Organization; 2014.

    Google Scholar 

  71. Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2016;4:CD002244. https://doi.org/10.1002/14651858.CD002244.pub4.

    PubMed  Google Scholar 

  72. Critchley JA, Young F, Orton L, Garner P. Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(3):223–37. https://doi.org/10.1016/S1473-3099(12)70321-3.

    Article  CAS  PubMed  Google Scholar 

  73. Kilincoglu BF, Dalkilic T, Dincbal MN, Aydin Y. Shunting in hydrocephalus due to tuberculous meningitis. Cases presenting with high cerebrospinal fluid proteins in pediatric age. J Neurosurg Sci. 2009;53(2):49–53.

    CAS  PubMed  Google Scholar 

  74. Misra UK, Kalita J, Nair PP. Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial. J Neurol Sci. 2010;293(1–2):12–7. https://doi.org/10.1016/j.jns.2010.03.025.

    Article  CAS  PubMed  Google Scholar 

  75. Schoeman JF, Janse van Rensburg A, Laubscher JA, Springer P. The role of aspirin in childhood tuberculous meningitis. J Child Neurol. 2011;26(8):956–62. https://doi.org/10.1177/0883073811398132.

    Article  PubMed  Google Scholar 

  76. Yang Z, Kong Y, Wilson F, Foxman B, Fowler AH, Marrs CF, et al. Identification of risk factors for extrapulmonary tuberculosis. Clin Infect Dis. 2004;38(2):199–205. https://doi.org/10.1086/380644.

    Article  PubMed  Google Scholar 

  77. Rajasingham R, Rhein J, Klammer K, Musubire A, Nabeta H, Akampurira A, et al. Epidemiology of meningitis in an HIV-infected Ugandan cohort. Am J Trop Med Hyg. 2015;92(2):274–9. https://doi.org/10.4269/ajtmh.14-0452.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Thwaites GE, Duc Bang N, Huy Dung N, Thi Quy H, Thi Tuong Oanh D, Thi Cam Thoa N, et al. The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with tuberculous meningitis. J Infect Dis. 2005;192(12):2134–41. https://doi.org/10.1086/498220.

    Article  PubMed  Google Scholar 

  79. Cecchini D, Ambrosioni J, Brezzo C, Corti M, Rybko A, Perez M, et al. Tuberculous meningitis in HIV-infected and non-infected patients: comparison of cerebrospinal fluid findings [short communication]. Int J Tuberc Lung Dis. 2009;13(2):269–71.

    CAS  PubMed  Google Scholar 

  80. Vidal J, Penalva de Oliveira A, Hernández A. CD4+ T-cell count and cerebrospinal fluid findings in HIV-infected patients with tuberculous meningitis [correspondence]. Int J Tuberc Lung Dis. 2010;14(11):1496–7.

    CAS  PubMed  Google Scholar 

  81. Puccioni-Sohler M, Brandão CO. Factors associated to the positive cerebrospinal fuid culture in the tuberculous meningitis. Arq Neuropsiquiatr. 2007;65(1):48–53.

    Article  PubMed  Google Scholar 

  82. Chamie G, Marquez C, Luetkemeyer A. HIV-associated central nervous system tuberculosis. Semin Neurol. 2014;34(1):103–15. https://doi.org/10.1055/s-0034-1372347.

    Article  PubMed  Google Scholar 

  83. Laureillard D, Marcy O, Madec Y, Chea S, Chan S, Borand L, et al. Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial. AIDS. 2013;27(16):2577–86. https://doi.org/10.1097/01.aids.0000432456.14099.c7.

    Article  CAS  PubMed  Google Scholar 

  84. Marais S, Meintjes G, Pepper DJ, Dodd LE, Schutz C, Ismail Z, et al. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2013;56(3):450–60. https://doi.org/10.1093/cid/cis899.

    Article  CAS  PubMed  Google Scholar 

  85. Pepper DJ, Marais S, Maartens G, Rebe K, Morroni C, Rangaka MX, et al. Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series. Clin Infect Dis. 2009;48(11):e96–107. https://doi.org/10.1086/598988.

    Article  PubMed  Google Scholar 

  86. Marais S, Wilkinson KA, Lesosky M, Coussens AK, Deffur A, Pepper DJ, et al. Neutrophil-associated central nervous system inflammation in tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2014;59(11):1638–47. https://doi.org/10.1093/cid/ciu641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Marais S, Lai RPJ, Wilkinson KA, Meintjes G, O'Garra A, Wilkinson RJ. Inflammasome activation underlying central nervous system deterioration in HIV-associated tuberculosis. J Infect Dis. 2017;215(5):677–86. https://doi.org/10.1093/infdis/jiw561.

    PubMed  Google Scholar 

  88. Meintjes G, Wilkinson RJ, Morroni C, Pepper DJ, Rebe K, Rangaka MX, et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2010;24(15):2381–90. https://doi.org/10.1097/QAD.0b013e32833dfc68.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Bell LC, Breen R, Miller RF, Noursadeghi M, Lipman M. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. Int J Infect Dis. 2015;32:39–45. https://doi.org/10.1016/j.ijid.2014.12.030.

    Article  CAS  PubMed  Google Scholar 

  90. Carvalho AC, De Iaco G, Saleri N, Pini A, Capone S, Manfrin M, et al. Paradoxical reaction during tuberculosis treatment in HIV-seronegative patients. Clin Infect Dis. 2006;42(6):893–5. https://doi.org/10.1086/500459.

    Article  CAS  PubMed  Google Scholar 

  91. Garg RK, Malhotra HS, Kumar N. Paradoxical reaction in HIV negative tuberculous meningitis. J Neurol Sci. 2014;340(1–2):26–36. https://doi.org/10.1016/j.jns.2014.03.025.

    Article  PubMed  Google Scholar 

  92. Geri G, Passeron A, Heym B, Arlet JB, Pouchot J, Capron L, et al. Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients. Infection. 2013;41(2):537–43. https://doi.org/10.1007/s15010-012-0376-9.

    Article  CAS  PubMed  Google Scholar 

  93. • Tai ML, Nor HM, Kadir KA, Viswanathan S, Rahmat K, Zain NR, et al. Paradoxical manifestation is common in HIV-negative tuberculous meningitis. Medicine (Baltimore). 2016;95(1):e1997. https://doi.org/10.1097/md.0000000000001997. This prospective study among HIV-uninfected persons at two centers in Malaysia evaluated the frequency of paradoxical worsening of TB meningitis after treatment initiation. This phenomenon occurred in more than half of the patients, with high rates of recurrence. The frequency was higher than previous estimates. New findings on neuroimaging and clinical deterioration were the most common features of paradoxical worsening.

    Article  Google Scholar 

  94. Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8(8):516–23.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697–706. https://doi.org/10.1056/NEJMoa0905848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med. 2011;365(16):1492–501. https://doi.org/10.1056/NEJMoa1014181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–91. https://doi.org/10.1056/NEJMoa1013607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kendall MA, Nyirenda M, Wu X, Ive P, Benson CA, Andersen JW, et al. Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity and implications for HIV-TB programs. J Acquir Immune Defic Syndr. 2014;65(4):423.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Naidoo K, Yende-Zuma N, Padayatchi N, Naidoo K, Jithoo N, Nair G, et al. The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: findings from the SAPiT trial. Ann Intern Med. 2012;157(5):313–24. https://doi.org/10.7326/0003-4819-157-5-201209040-00004.

    Article  PubMed  PubMed Central  Google Scholar 

  100. •• Torok ME, Yen NT, Chau TT, Mai NT, Phu NH, Mai PP, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis. Clin Infect Dis. 2011;52(11):1374–83. https://doi.org/10.1093/cid/cir230. After a large study from South Africa of HIV-infected TB patients demonstrated unequivocally that early initiation of antiretroviral therapy (ART) dramatically improved survival, this study evaluated whether a similar strategy could be applied to patients with TB meningitis. In a randomized, double-blind, placebo-controlled trial, patients living with HIV and diagnosed with TB meningitis were randomized to start ART within 7 days of TB treatment or after 2 months of TB treatment. Immediate ART in patients with TB meningitis did not improve survival, and was associated with higher risk of adverese events.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Makadzange AT, Ndhlovu CE, Takarinda K, Reid M, Kurangwa M, Gona P, et al. Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin Infect Dis. 2010;50(11):1532–8. https://doi.org/10.1086/652652.

    Article  CAS  PubMed  Google Scholar 

  102. Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, Musubire A, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. 2014;370(26):2487–98. https://doi.org/10.1056/NEJMoa1312884.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kassem Bourgi.

Ethics declarations

Conflict of Interest

Drs Bourgi, Fiske and Sterling declare no conflict of interests.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards.

Additional information

This article is part of the Topical Collection on Central Nervous System Infections

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bourgi, K., Fiske, C. & Sterling, T.R. Tuberculosis Meningitis. Curr Infect Dis Rep 19, 39 (2017). https://doi.org/10.1007/s11908-017-0595-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11908-017-0595-4

Keywords

Navigation