Bacterial meningitis in Africa

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus), Escherichia coli, and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.

[1]  T. Lamagni,et al.  Incidence and aetiology of infant Gram-negative bacteraemia and meningitis: systematic review and meta-analysis , 2022, Archives of Disease in Childhood.

[2]  F. Petronilho,et al.  Dysfunctional Glymphatic System with Disrupted Aquaporin 4 Expression Pattern on Astrocytes Causes Bacterial Product Accumulation in the CSF during Pneumococcal Meningitis , 2022, bioRxiv.

[3]  Jun Zhang,et al.  Homologous Escherichia coli Identified in Cerebrospinal Fluid and Bloodstream , 2021, Frontiers in Cellular and Infection Microbiology.

[4]  R. Solomons,et al.  The use of thalidomide to treat children with tuberculosis meningitis: A review. , 2021, Tuberculosis.

[5]  Lee E. Korshoj,et al.  The Prospect of Nanoparticle Systems for Modulating Immune Cell Polarization During Central Nervous System Infection , 2021, Frontiers in Immunology.

[6]  Moo-Seung Lee,et al.  Escherichia coli Shiga Toxins and Gut Microbiota Interactions , 2021, Toxins.

[7]  L. Dodd,et al.  Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM] , 2021, Wellcome open research.

[8]  Varinder Singh,et al.  Defeating Paediatric Tuberculous Meningitis: Applying the WHO “Defeating Meningitis by 2030: Global Roadmap” , 2021, Microorganisms.

[9]  D. Kathayat,et al.  Avian Pathogenic Escherichia coli (APEC): An Overview of Virulence and Pathogenesis Factors, Zoonotic Potential, and Control Strategies , 2021, Pathogens.

[10]  J. Widengren,et al.  Neuronal death in pneumococcal meningitis is triggered by pneumolysin and RrgA interactions with β-actin , 2021, PLoS pathogens.

[11]  T. Iype,et al.  Neurotuberculosis: an update , 2021, Acta Neurologica Belgica.

[12]  C. Whitney,et al.  Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006–18: prospective observational time-series and case-control studies , 2020, The Lancet. Global health.

[13]  R. Hasbún,et al.  Management of Acute Bacterial Meningitis in Children , 2020, Infection and drug resistance.

[14]  Xiang-Qi Tang,et al.  Detection of Listeria monocytogenes in a patient with meningoencephalitis using next-generation sequencing: a case report , 2020, BMC Infectious Diseases.

[15]  E. Tucker,et al.  International Survey Reveals Opportunities to Improve Tuberculous Meningitis Management and the Need for Standardized Guidelines , 2020, Open forum infectious diseases.

[16]  E. Denamur,et al.  The population genetics of pathogenic Escherichia coli , 2020, Nature Reviews Microbiology.

[17]  M. Gil,et al.  Actin Assembly around the Shigella-Containing Vacuole Promotes Successful Infection , 2020, Cell reports.

[18]  S. Normark,et al.  The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease , 2020, Molecular microbiology.

[19]  D. Briles,et al.  New Strategy Is Needed to Prevent Pneumococcal Meningitis , 2020, The Pediatric infectious disease journal.

[20]  B. Schmand,et al.  Long-term neurological and cognitive outcome, and quality of life in adults after pneumococcal meningitis. , 2020, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[21]  R. Geskus,et al.  Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study , 2020, The Lancet. Infectious diseases.

[22]  D. Boulware,et al.  Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study , 2020, The Lancet. Infectious diseases.

[23]  R. Zhou,et al.  DAMP-sensing receptors in sterile inflammation and inflammatory diseases , 2019, Nature Reviews Immunology.

[24]  J. Lewnard,et al.  Dose-specific effectiveness of 7- and 13-valent pneumococcal conjugate vaccines against vaccine-serotype Streptococcus pneumoniae colonization in children. , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  Ryan T Novak,et al.  Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017. , 2019, The Journal of infectious diseases.

[26]  R. Wilkinson,et al.  Key considerations in the pharmacotherapy of tuberculous meningitis , 2019, Expert opinion on pharmacotherapy.

[27]  Juno Thomas,et al.  Outbreak of Listeria monocytogenes in South Africa, 2017–2018: Laboratory Activities and Experiences Associated with Whole-Genome Sequencing Analysis of Isolates , 2019, Foodborne pathogens and disease.

[28]  G. Hummer,et al.  Membrane perforation by the pore-forming toxin pneumolysin , 2019, Proceedings of the National Academy of Sciences.

[29]  Jian-qing He,et al.  Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis , 2019, BMC Pulmonary Medicine.

[30]  D. Boulware,et al.  Inadequate diagnostics: the case to move beyond the bacilli for detection of meningitis due to Mycobacterium tuberculosis. , 2019, Journal of medical microbiology.

[31]  K. Stanley,et al.  Application of Cerebrospinal Fluid Host Protein Biosignatures in the Diagnosis of Tuberculous Meningitis in Children from a High Burden Setting , 2019, Mediators of inflammation.

[32]  B. Henriques-Normark,et al.  The Role of Microglia in Bacterial Meningitis: Inflammatory Response, Experimental Models and New Neuroprotective Therapeutic Strategies , 2019, Front. Microbiol..

[33]  H. Welch,et al.  Epidemiology of bacterial meningitis in children admitted to Gondar University Hospital in the post pneumococcal vaccine era , 2018, The Pan African medical journal.

[34]  J. Forrester,et al.  CNS infection and immune privilege , 2018, Nature Reviews Neuroscience.

[35]  A. Walker,et al.  Trends over time in Escherichia coli bloodstream infections, urinary tract infections, and antibiotic susceptibilities in Oxfordshire, UK, 1998-2016: a study of electronic health records. , 2018, The Lancet. Infectious diseases.

[36]  H. Lopardo,et al.  Susceptibility to β-lactams in β-hemolytic streptococci. , 2018, Revista Argentina de microbiologia.

[37]  M. Anand,et al.  Community-acquired Escherichia coli meningitis with ventriculitis in an adult—a rare case report , 2018, Journal of Intensive Care.

[38]  B. Henriques-Normark,et al.  Receptor Blockade: A Novel Approach to Protect the Brain From Pneumococcal Invasion , 2018, The Journal of infectious diseases.

[39]  A. van der Ende,et al.  Community-acquired meningitis in adults caused by Escherichia coli in Denmark and The Netherlands. , 2018, The Journal of infection.

[40]  R. Geskus,et al.  Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial , 2018, Wellcome open research.

[41]  R. Geskus,et al.  A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults , 2018, eLife.

[42]  M. Brouwer,et al.  Epidemiology of community-acquired bacterial meningitis , 2018, Current opinion in infectious diseases.

[43]  P. Cossart,et al.  Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis , 2017, Nature Reviews Microbiology.

[44]  R. Geskus,et al.  Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial. , 2018, Wellcome open research.

[45]  Mohammad Hossein Khosravi,et al.  Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2017, Lancet.

[46]  J. A. Woenig,et al.  The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury , 2017, International journal of molecular sciences.

[47]  A. van der Ende,et al.  Listeria monocytogenes meningitis in the Netherlands, 1985–2014: A nationwide surveillance study , 2017, The Journal of infection.

[48]  E. D. Khilazheva,et al.  Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit , 2017, Front. Cell. Infect. Microbiol..

[49]  A. van der Ende,et al.  pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion , 2017, The Journal of experimental medicine.

[50]  P. Ravaud,et al.  Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. , 2017, The Lancet. Infectious diseases.

[51]  M. Brouwer,et al.  MONALISA: a grim picture of listeriosis. , 2017, The Lancet. Infectious diseases.

[52]  S. Bentley,et al.  Benzalkonium tolerance genes and outcome in Listeria monocytogenes meningitis , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[53]  L. Vaz Meningococcal Disease , 2017, Pediatrics in Review.

[54]  A. Michelucci,et al.  Cellular and Molecular Characterization of Microglia: A Unique Immune Cell Population , 2017, Front. Immunol..

[55]  I. Galea,et al.  The blood-brain barrier in systemic inflammation , 2017, Brain, Behavior, and Immunity.

[56]  Manoj Kumar,et al.  INGE GRUNDKE-IQBAL AWARD FOR ALZHEIMER’S RESEARCH: NEUROTOXIC REACTIVE ASTROCYTES ARE INDUCED BY ACTIVATED MICROGLIA , 2019, Alzheimer's & Dementia.

[57]  R. Heyderman,et al.  Prediction of Outcome From Adult Bacterial Meningitis in a High-HIV-Seroprevalence, Resource-Poor Setting Using the Malawi Adult Meningitis Score (MAMS) , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[58]  H. Forssberg,et al.  The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior , 2016, Molecular Psychiatry.

[59]  C. Whitney,et al.  Community-acquired bacterial meningitis , 2016, Nature Reviews Disease Primers.

[60]  H. Pfister,et al.  Dramatic reduction of mortality in pneumococcal meningitis , 2016, Critical Care.

[61]  N. Wieselthaler,et al.  Imaging Features of the Brain, Cerebral Vessels and Spine in Pediatric Tuberculous Meningitis With Associated Hydrocephalus , 2016, The Pediatric infectious disease journal.

[62]  N. Govender,et al.  The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012 , 2016, PloS one.

[63]  S. Nadel Treatment of Meningococcal Disease. , 2016, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[64]  Geneviève Garriss,et al.  Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA. , 2016, The Journal of clinical investigation.

[65]  O. Cars,et al.  UN High-Level Meeting on antimicrobials—what do we need? , 2016, The Lancet.

[66]  M. Brouwer,et al.  Neurological sequelae of bacterial meningitis. , 2016, The Journal of infection.

[67]  J. Vazquez,et al.  Global Meningococcal Initiative: guidelines for diagnosis and confirmation of invasive meningococcal disease , 2016, Epidemiology and Infection.

[68]  K. Carroll,et al.  Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens , 2016, Journal of Clinical Microbiology.

[69]  J. V. van Dijl,et al.  How Does Streptococcus pneumoniae Invade the Brain? , 2016, Trends in microbiology.

[70]  N. Beeching,et al.  The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. , 2016, The Journal of infection.

[71]  Mamta B. Singh,et al.  Corticosteroids for managing tuberculous meningitis , 2016, The Cochrane database of systematic reviews.

[72]  B. Baban,et al.  Blood–brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[73]  A. van der Ende,et al.  Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. , 2016, The Lancet. Infectious diseases.

[74]  A. Figaji,et al.  Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus , 2016, Developmental medicine and child neurology.

[75]  K. Ishida,et al.  Spontaneous Escherichia coli bacterial meningitis mimicking heatstroke in an adult , 2016, Clinical case reports.

[76]  A. Lindstrand,et al.  Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden , 2016, European Respiratory Journal.

[77]  Franziska Wulf,et al.  Immunology A Short Course , 2016 .

[78]  J. Quevedo,et al.  Role of Microglial Activation in the Pathophysiology of Bacterial Meningitis , 2016, Molecular Neurobiology.

[79]  M. Brouwer,et al.  Corticosteroids for acute bacterial meningitis. , 2015, The Cochrane database of systematic reviews.

[80]  S. Esposito,et al.  Meningococcal disease in childhood: epidemiology, clinical features and prevention , 2015, Journal of preventive medicine and hygiene.

[81]  Q. Dube,et al.  Improving the outcome of bacterial meningitis in newborn infants in Africa: reflections on recent progress , 2015, Current opinion in infectious diseases.

[82]  Christopher Gilpin,et al.  WHO's new End TB Strategy , 2015, The Lancet.

[83]  R. Rappuoli,et al.  Neisseria meningitidis: pathogenesis and immunity. , 2015, Current opinion in microbiology.

[84]  J. Frade,et al.  Neuronal cell cycle: the neuron itself and its circumstances , 2015, Cell cycle.

[85]  M. Kalin,et al.  Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types , 2014, European Respiratory Journal.

[86]  A. Benedetti,et al.  Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis. , 2014, The Lancet. Infectious diseases.

[87]  Tami D. Lieberman,et al.  Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance , 2014, Proceedings of the National Academy of Sciences.

[88]  D. Granoff,et al.  Human Factor H (FH) Impairs Protective Meningococcal Anti-FHbp Antibody Responses and the Antibodies Enhance FH Binding , 2014, mBio.

[89]  Jon C. Aster,et al.  Robbins & Cotran Pathologic Basis of Disease , 2014 .

[90]  J. Quevedo,et al.  Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis. , 2014, Revista brasileira de psiquiatria.

[91]  A. van der Ende,et al.  Cerebrospinal fluid inflammatory markers in patients with Listeria monocytogenes meningitis , 2014, BBA clinical.

[92]  A. van der Ende,et al.  Outcome in patients with bacterial meningitis presenting with a minimal Glasgow Coma Scale score , 2014, Neurology: Neuroimmunology & Neuroinflammation.

[93]  Yu-Qiang Ding,et al.  Minocycline and Risperidone Prevent Microglia Activation and Rescue Behavioral Deficits Induced by Neonatal Intrahippocampal Injection of Lipopolysaccharide in Rats , 2014, PloS one.

[94]  M. Molyneux,et al.  Bacterial Meningitis in Malawian Adults, Adolescents, and Children During the Era of Antiretroviral Scale-up and Haemophilus influenzae Type b Vaccination, 2000–2012 , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[95]  T. van der Poll,et al.  Host innate immune responses to sepsis , 2013, Virulence.

[96]  S. Heckenberg,et al.  Bacterial meningitis. , 2014, Handbook of clinical neurology.

[97]  J. Luo,et al.  Phagocytosis of Microglia in the Central Nervous System Diseases , 2014, Molecular Neurobiology.

[98]  A. Teixeira,et al.  Pathophysiology of neonatal acute bacterial meningitis. , 2013, Journal of medical microbiology.

[99]  B. Stoll,et al.  Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010 , 2013, Pediatric Research.

[100]  Johan Schoeman,et al.  Tuberculous meningitis: more questions, still too few answers , 2013, The Lancet Neurology.

[101]  P. Coll,et al.  Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome , 2013, BMC Infectious Diseases.

[102]  Z. Bhutta,et al.  Global epidemiology of invasive meningococcal disease , 2013, Population Health Metrics.

[103]  O. Yeǧin,et al.  Escherichia coli brain abscess in a twin pair associated with TLR4 gene mutation , 2013, Pediatrics international : official journal of the Japan Pediatric Society.

[104]  S. Leib,et al.  Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis , 2013, BMC Infectious Diseases.

[105]  G. Molema,et al.  University of Groningen Interactions between Blood-Borne Streptococcus pneumoniae and the Blood-Brain Barrier Preceding Meningitis , 2018 .

[106]  A. van der Ende,et al.  Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[107]  H. Kumar,et al.  Recognition of bacterial infection by innate immune sensors , 2013, Critical reviews in microbiology.

[108]  B. Wren,et al.  Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli , 2013, Infection and Immunity.

[109]  H. Luma,et al.  Tuberculous meningitis: presentation, diagnosis and outcome in hiv-infected patients at the douala general hospital, cameroon: a cross sectional study , 2013, AIDS Research and Therapy.

[110]  G. Molema,et al.  Signalling or binding: the role of the platelet‐activating factor receptor in invasive pneumococcal disease , 2013, Cellular microbiology.

[111]  S. Salekeen,et al.  Clinical course, complications and predictors of mortality in patients with tuberculous meningitis--an experience of fifty two cases at Civil Hospital Karachi, Pakistan. , 2013, JPMA. The Journal of the Pakistan Medical Association.

[112]  A. Mildner,et al.  Resistance of the Brain to Escherichia coli K1 Infection Depends on MyD88 Signaling and the Contribution of Neutrophils and Monocytes , 2013, Infection and Immunity.

[113]  P. Coll,et al.  The spectrum of acute bacterial meningitis in elderly patients , 2013, BMC Infectious Diseases.

[114]  V. Perry,et al.  Review: Activation patterns of microglia and their identification in the human brain , 2013, Neuropathology and applied neurobiology.

[115]  E. Kashibu,et al.  Bacterial isolates from cerebrospinal fluid of children with suspected acute meningitis in a Nigerian tertiary hospital. , 2013, The Nigerian postgraduate medical journal.

[116]  A. Ramzan,et al.  Childhood tubercular meningitis: an institutional experience and analysis of predictors of outcome. , 2013, Pediatric neurology.

[117]  O. Baud,et al.  Neonatal bacterial meningitis. , 2013, Handbook of clinical neurology.

[118]  Tengda Xu,et al.  Community acquired Listeria monocytogenes meningitis in adults , 2012 .

[119]  R. Ransohoff,et al.  Inflammatory cell trafficking across the blood–brain barrier: chemokine regulation and in vitro models , 2012, Immunological reviews.

[120]  K. Kim Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention , 2012, Current opinion in infectious diseases.

[121]  A. M. van Furth,et al.  Seasonal variation in the incidence rate of tuberculous meningitis is associated with sunshine hours , 2012, Epidemiology and Infection.

[122]  V. Vaillant,et al.  Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[123]  N. Rouphael,et al.  Neisseria meningitidis: biology, microbiology, and epidemiology. , 2012, Methods in molecular biology.

[124]  S. Nomura,et al.  Fulminant Tuberculous Meningitis , 2012 .

[125]  Nicholas A. Be,et al.  Role of Mycobacterium tuberculosis pknD in the Pathogenesis of central nervous system tuberculosis , 2012, BMC Microbiology.

[126]  M. Lipsitch,et al.  Serotype replacement in disease after pneumococcal vaccination , 2011, The Lancet.

[127]  W. Pan,et al.  Cytokine signaling modulates blood-brain barrier function. , 2011, Current pharmaceutical design.

[128]  P. Berche,et al.  Diagnosis of Listeria monocytogenes Meningoencephalitis by Real-Time PCR for the hly Gene , 2011, Journal of Clinical Microbiology.

[129]  Diederik van de Beek,et al.  Pathogenesis and Pathophysiology of Pneumococcal Meningitis , 2011, Clinical Microbiology Reviews.

[130]  O. Swann,et al.  Systematic review: neonatal meningitis in the developing world , 2011, Tropical medicine & international health : TM & IH.

[131]  J. Laubscher,et al.  The Role of Aspirin in Childhood Tuberculous Meningitis , 2011, Journal of child neurology.

[132]  Aruna Chandran,et al.  Long-term Sequelae of Childhood Bacterial Meningitis: An Underappreciated Problem , 2011, The Pediatric infectious disease journal.

[133]  Guy Thwaites,et al.  Tuberculous meningitis: a uniform case definition for use in clinical research. , 2010, The Lancet. Infectious diseases.

[134]  A. Figaji,et al.  The neurosurgical and acute care management of tuberculous meningitis: evidence and current practice. , 2010, Tuberculosis.

[135]  B. Robertson,et al.  The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis. , 2010, Tuberculosis.

[136]  G. Sengoz,et al.  Predictors of mortality in tuberculous meningitis: a multivariate analysis of 160 cases. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[137]  F. Sörgel,et al.  Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections , 2010, Clinical Microbiology Reviews.

[138]  R. Nau,et al.  Mechanisms of injury in bacterial meningitis , 2010, Current opinion in neurology.

[139]  I. Rudan,et al.  Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. , 2010, The Lancet. Infectious diseases.

[140]  Chien-Chang Yang,et al.  Prognostic factors of tuberculous meningitis in adults: a 6-year retrospective study at a tertiary hospital in northern Taiwan. , 2010, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[141]  A. Iwasaki,et al.  Regulation of Adaptive Immunity by the Innate Immune System , 2010, Science.

[142]  S. Leib,et al.  Pathogenesis and pathophysiology of bacterial CNS infections. , 2010, Handbook of clinical neurology.

[143]  K. Kim Acute bacterial meningitis in infants and children. , 2010, The Lancet. Infectious diseases.

[144]  J. Weber,et al.  Review: Pathophysiology and treatment of bacterial meningitis , 2009, Therapeutic advances in neurological disorders.

[145]  O. Levine,et al.  Sequelae due to bacterial meningitis among African children: a systematic literature review , 2009, BMC medicine.

[146]  T. Cherian,et al.  Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates , 2009, The Lancet.

[147]  P. Donald,et al.  Tuberculous cerebrovascular disease: a review. , 2009, The Journal of infection.

[148]  V. Nizet,et al.  The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion , 2009, The Journal of experimental medicine.

[149]  E. Tuomanen,et al.  Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. , 2009, The Journal of clinical investigation.

[150]  S. Akira Innate immunity to pathogens: diversity in receptors for microbial recognition , 2009, Immunological reviews.

[151]  C. Terwee,et al.  Twenty Years of Pediatric Tuberculous Meningitis: A Retrospective Cohort Study in the Western Cape of South Africa , 2009, Pediatrics.

[152]  A. Mildner,et al.  Toll-Like Receptor Prestimulation Increases Phagocytosis of Escherichia coli DH5α and Escherichia coli K1 Strains by Murine Microglial Cells , 2008, Infection and Immunity.

[153]  H. Wagner,et al.  Innate immunity to pneumococcal infection of the central nervous system depends on toll-like receptor (TLR) 2 and TLR4. , 2008, The Journal of infectious diseases.

[154]  J. Luzio,et al.  Differential expression of the polysialyl capsule during blood-to-brain transit of neuropathogenic Escherichia coli K1. , 2008, Microbiology.

[155]  K. Kim Mechanisms of microbial traversal of the blood–brain barrier , 2008, Nature Reviews Microbiology.

[156]  P. Reiss,et al.  Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. , 2008, The Lancet. Infectious diseases.

[157]  M. J. Simões,et al.  Molecular surveillance of Neisseria meningitidis capsular switching in Portugal, 2002–2006 , 2008, Epidemiology and Infection.

[158]  A. Chan,et al.  A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies , 2008, The Journal of experimental medicine.

[159]  T. Molitor,et al.  Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects , 2008, Clinical Microbiology Reviews.

[160]  J. Farrar,et al.  The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis , 2008, PLoS pathogens.

[161]  C. Whitty,et al.  Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. , 2007, The New England journal of medicine.

[162]  R. Rappuoli,et al.  RrgA is a pilus-associated adhesin in Streptococcus pneumoniae , 2007, Molecular microbiology.

[163]  B. Greenwood,et al.  Epidemic meningitis, meningococcaemia, and Neisseria meningitidis , 2007, The Lancet.

[164]  G. Marks,et al.  A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. , 2007, American journal of respiratory and critical care medicine.

[165]  T. Mcintosh,et al.  The duality of the inflammatory response to traumatic brain injury , 2001, Molecular Neurobiology.

[166]  S. Heckenberg,et al.  Community-acquired Listeria monocytogenes meningitis in adults. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[167]  L. Zhao,et al.  A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. , 2006, The Journal of infectious diseases.

[168]  Guy Thwaites,et al.  Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with Human Immunodeficiency Virus Infection and Multidrug Resistance in Cases of Tuberculous Meningitis , 2006, Journal of Clinical Microbiology.

[169]  Etienne Carbonnelle,et al.  A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili , 2006, Molecular microbiology.

[170]  W. Banks,et al.  Release of cytokines by brain endothelial cells: A polarized response to lipopolysaccharide , 2006, Brain, Behavior, and Immunity.

[171]  A. Charbit,et al.  Listeriolysin O: a key protein of Listeria monocytogenes with multiple functions. , 2006, FEMS microbiology reviews.

[172]  W. Bishai,et al.  Mycobacterium tuberculosis invasion and traversal across an in vitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis. , 2006, The Journal of infectious diseases.

[173]  M. Mendelson,et al.  Intractable Intracranial Tuberculous Infection Responsive to Thalidomide: Report of Four Cases , 2006, Journal of child neurology.

[174]  L. Peterson Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter? , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[175]  Allan R Tunkel,et al.  Community-acquired bacterial meningitis in adults. , 2006, The New England journal of medicine.

[176]  D. Hamer,et al.  Rapid Diagnosis of Pneumococcal Meningitis: Implications for Treatment and Measuring Disease Burden , 2005, The Pediatric infectious disease journal.

[177]  A. Blom,et al.  Binding of the Complement Inhibitor C4bp to Serogroup B Neisseria meningitidis 1 , 2005, The Journal of Immunology.

[178]  Liem Nguyen,et al.  The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. , 2005, Trends in cell biology.

[179]  P. Donald,et al.  Tuberculous meningitis and miliary tuberculosis: the Rich focus revisited. , 2005, The Journal of infection.

[180]  B. Genton,et al.  Cerebrospinal fluid lactate in 78 cases of adult meningitis , 2005, Intensive Care Medicine.

[181]  P. Andrew,et al.  The role of pneumolysin in pneumococcal pneumonia and meningitis , 2004, Clinical and experimental immunology.

[182]  Martijn Weisfelt,et al.  Clinical features and prognostic factors in adults with bacterial meningitis. , 2004, The New England journal of medicine.

[183]  Raj Kumar,et al.  Tuberculous brain stem abscesses in children , 2004, Journal of Pediatric Neurology.

[184]  P. Haslett,et al.  Adjunctive Thalidomide Therapy for Childhood Tuberculous Meningitis: Results of a Randomized Study , 2004, Journal of child neurology.

[185]  D. Drevets,et al.  Invasion of the Central Nervous System by Intracellular Bacteria , 2004, Clinical Microbiology Reviews.

[186]  J. Kimpen,et al.  Tuberculous meningitis and miliary tuberculosis in young children , 2004, Tropical medicine & international health : TM & IH.

[187]  Harry L. T. Mobley,et al.  Pathogenic Escherichia coli , 2004, Nature Reviews Microbiology.

[188]  J. Chung,et al.  Outer membrane protein A and cytotoxic necrotizing factor-1 use diverse signaling mechanisms for Escherichia coli K1 invasion of human brain microvascular endothelial cells. , 2003, Microbial pathogenesis.

[189]  G. Overturf Indications for the immunological evaluation of patients with meningitis. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[190]  Clar Ni Chonghaile Meningitis in Africa—tackling W135 , 2002, The Lancet.

[191]  H. Pfister,et al.  Pathogenesis and pathophysiology of pneumococcal meningitis. , 2002, The Lancet. Infectious diseases.

[192]  P. Donald,et al.  Long‐term follow up of childhood tuberculous meningitis , 2002 .

[193]  F. Quinn,et al.  Demonstration of spread by Mycobacterium tuberculosis bacilli in A549 epithelial cell monolayers. , 2002, FEMS microbiology letters.

[194]  J. Chung,et al.  Cytotoxic Necrotizing Factor-1 Contributes to Escherichia coli K1 Invasion of the Central Nervous System* , 2002, The Journal of Biological Chemistry.

[195]  C.-H. Lu,et al.  The Prognostic Factors of Adult Tuberculous Meningitis , 2001, Infection.

[196]  P. Boquet The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. , 2001, Toxicon : official journal of the International Society on Toxinology.

[197]  A. Fruth,et al.  Enterohemorrhagic Escherichia coli. , 2001, Contributions to microbiology.

[198]  P. Haslett,et al.  Adjunctive Thalidomide Therapy of Childhood Tuberculous Meningitis: Possible Anti-Inflammatory Role , 2000, Journal of child neurology.

[199]  V. Novelli,et al.  Tuberculosis of the central nervous system in children: a 20-year survey. , 2000, The Journal of infection.

[200]  Virji The structural basis of CEACAM-receptor targeting by neisserial opa proteins: response , 2000, Trends in microbiology.

[201]  D. Briles,et al.  The pspC Gene of Streptococcus pneumoniae Encodes a Polymorphic Protein, PspC, Which Elicits Cross-Reactive Antibodies to PspA and Provides Immunity to Pneumococcal Bacteremia , 1999, Infection and Immunity.

[202]  K. Haspolat,et al.  Central Nervous System Tuberculosis in Children: A Review of 214 Cases , 1998, Pediatrics.

[203]  E. Mylonakis,et al.  Central Nervous System Infection with Listeria monocytogenes : 33 Years' Experience at a General Hospital and Review of 776 Episodes from the Literature , 1998, Medicine.

[204]  E. Tuomanen,et al.  PAf receptor anchors Streptococcus pneumoniae to activated human endothelial cells. , 1996, Advances in experimental medicine and biology.

[205]  P. Donald,et al.  Serial CT Scanning in Childhood Tuberculous Meningitis: Prognostic Features in 198 Cases , 1995, Journal of child neurology.

[206]  P. Udani,et al.  Pathology and pathogenetic mechanisms in neurotuberculosis. , 1995, Radiologic clinics of North America.

[207]  V. Caviness,et al.  Acute bacterial meningitis in adults. A review of 493 episodes. , 1993, The New England journal of medicine.

[208]  P. Donald,et al.  Cerebrospinal fluid investigations in tuberculous meningitis. , 1991, Annals of tropical paediatrics.

[209]  R. Fallon,et al.  LISTERIOSIS , 1985, The Lancet.

[210]  M. Achtman,et al.  Induction of bacteremia in newborn rats by Escherichia coli K1 is correlated with only certain O (lipopolysaccharide) antigen types , 1983, Infection and immunity.

[211]  N. Niles Pathologic Basis of Disease , 1974 .

[212]  H. V. Smith TUBERCULOUS MENINGITIS. , 1964, International journal of neurology.

[213]  P. Daniel Gross Morbid Anatomy of the Central Nervous System of Cases of Tuberculous Meningitis Treated with Streptomycin , 1949, Proceedings of the Royal Society of Medicine.

[214]  W. Wood,et al.  Acute meningitis. , 1947, The American journal of medicine.

[215]  K. Shadan,et al.  Available online: , 2012 .