Details of Disease

General Information of Disease (ID: DISM5U0L)

• Disease Name: Pneumococcal meningitis
• Synonyms: Streptococcus pneumoniae caused infectious meningitis; Streptococcus pneumoniae infectious meningitis
• Definition: An acute purulent infection of the meninges and subarachnoid space caused by Streptococcus pneumoniae, most prevalent in children and adults over the age of 60. This illness may be associated with otitis media; mastoiditis; sinusitis; respiratory tract infections; sickle cell disease (anemia, sickle cell); skull fractures; and other disorders. Clinical manifestations include fever; headache; neck stiffness; and somnolence followed by seizures; focal neurologic deficits (notably deafness); and coma. (From Miller et al., Merritt's Textbook of Neurology, 9th ed, p111)
• Disease Hierarchy:
  DISQ4DO4: Infectious meningitis
  DISQ65JM: Streptococcal meningitis
  DIS6SXQD: Pneumococcal infection
  DISM5U0L: Pneumococcal meningitis
• Disease Identifiers:
  MONDO ID: MONDO_0006913
  MESH ID: D008586
  UMLS CUI: C0025295
  MedGen ID: 44354
  Orphanet ID: 55655
  SNOMED CT ID: 51169003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Ampicillin	DMHWE7P	Approved	Small molecular drug	[1]
Ceftriaxone	DMCEW64	Approved	Small molecular drug	[2]
Meropenem	DM62UHC	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Benzylpenicillin	DMS9503	Phase 3	Small molecular drug	[4]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADAM17	TT6AZXG	Limited	Therapeutic	[5]
CD276	TT6CQUM	Limited	Biomarker	[6]
IRAK4	TTILUKB	Limited	Genetic Variation	[7]
ROS1	TTSZ6Y3	Limited	Genetic Variation	[8]
CAMP	TTULOB6	Strong	Biomarker	[9]
CXCL1	TTLK1RW	Strong	Biomarker	[10]
KYNU	TTWQM3J	Strong	Biomarker	[11]
LGALS3	TTFPQV7	Strong	Biomarker	[12]
MASP2	TTR01E9	Strong	Biomarker	[13]
NTRK2	TTKN7QR	Strong	Biomarker	[14]
P2RY6	TTNVSKA	Strong	Biomarker	[15]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PRF1	OTFVXD7H	Limited	Biomarker	[16]
STK32C	OTN4HBAA	Limited	Genetic Variation	[8]
TBC1D22A	OTP3JJLW	Limited	Genetic Variation	[8]
CBFA2T2	OTNOIB23	Strong	Biomarker	[17]
CCDC33	OTOIFZ4R	Strong	Genetic Variation	[8]
EXOC6B	OTFI1IPG	Strong	Genetic Variation	[18]
LGALS9	OT7MF91K	Strong	Biomarker	[12]
PIGR	OT6GLSUL	Strong	Biomarker	[19]
PPP1R12C	OT9Q86JO	Strong	Biomarker	[17]
PPP1R13B	OTC88VQO	Strong	Biomarker	[17]
RAET1E	OTLR3CEC	Strong	Biomarker	[20]
RELA	OTUJP9CN	Strong	Biomarker	[6]
SFTPA2	OT6SFOMU	Strong	Biomarker	[21]
NFKBIE	OTLAYEL9	Definitive	Genetic Variation	[22]

References

• [1] Ampicillin FDA Label
• [2] Ceftriaxone FDA Label
• [3] Meropenem FDA Label
• [4] Meningitis in adults: diagnosis and management. Intern Med J. 2018 Nov;48(11):1294-1307.
• [5] Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8.
• [6] B7-H3 Augments Inflammatory Responses and Exacerbates Brain Damage via Amplifying NF-B p65 and MAPK p38 Activation during Experimental Pneumococcal Meningitis.PLoS One. 2017 Jan 31;12(1):e0171146. doi: 10.1371/journal.pone.0171146. eCollection 2017.
• [7] Variation of 46 Innate Immune Genes Evaluated for their Contribution in Pneumococcal Meningitis Susceptibility and Outcome.EBioMedicine. 2016 Aug;10:77-84. doi: 10.1016/j.ebiom.2016.07.011. Epub 2016 Jul 12.
• [8] Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.Nat Commun. 2019 May 15;10(1):2176. doi: 10.1038/s41467-019-09976-3.
• [9] Expression and regulation of antimicrobial peptide rCRAMP after bacterial infection in primary rat meningeal cells.J Neuroimmunol. 2009 Dec 10;217(1-2):55-64. doi: 10.1016/j.jneuroim.2009.10.004. Epub 2009 Oct 30.
• [10] A kinetic study of the cytokine/chemokines levels and disruption of blood-brain barrier in infant rats after pneumococcal meningitis.J Neuroimmunol. 2011 Apr;233(1-2):12-7. doi: 10.1016/j.jneuroim.2010.10.035. Epub 2010 Nov 24.
• [11] The cerebral protective effect and mechanism of action of vitamin B6 adjuvant ceftriaxone in experimental pneumococcal meningitis.Brain Res. 2018 Sep 15;1695:53-64. doi: 10.1016/j.brainres.2018.05.031. Epub 2018 May 22.
• [12] Gene and protein expression of galectin-3 and galectin-9 in experimental pneumococcal meningitis.Neurobiol Dis. 2007 Nov;28(2):175-83. doi: 10.1016/j.nbd.2007.07.005. Epub 2007 Jul 10.
• [13] Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.J Neuroinflammation. 2017 Jan 3;14(1):2. doi: 10.1186/s12974-016-0770-9.
• [14] Dynamic changes of TrkB gene expression in Streptococcus pneumoniae meningitis after treatment with antibiotics and dexamethasone.World J Pediatr. 2011 Aug;7(3):250-6. doi: 10.1007/s12519-011-0285-5. Epub 2011 May 20.
• [15] Role of purinergic signaling in experimental pneumococcal meningitis.Sci Rep. 2017 Mar 16;7:44625. doi: 10.1038/srep44625.
• [16] Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia.J Neuroinflammation. 2019 May 18;16(1):105. doi: 10.1186/s12974-019-1491-7.
• [17] Brain-targeted delivery of PEGylated nano-bacitracin A against Penicillin-sensitive and -resistant Pneumococcal meningitis: formulated with RVG(29) and Pluronic() P85 unimers.Drug Deliv. 2018 Nov;25(1):1886-1897. doi: 10.1080/10717544.2018.1486473.
• [18] Exome Array Analysis of Susceptibility to Pneumococcal Meningitis.Sci Rep. 2016 Jul 8;6:29351. doi: 10.1038/srep29351.
• [19] pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion.J Exp Med. 2017 Jun 5;214(6):1619-1630. doi: 10.1084/jem.20161668. Epub 2017 May 17.
• [20] V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.Acta Neuropathol Commun. 2016 May 18;4(1):50. doi: 10.1186/s40478-016-0320-9.
• [21] Genetic diversity of pneumococcal surface protein A of Streptococcus pneumoniae meningitis in German children.Vaccine. 2007 Jan 22;25(6):1030-5. doi: 10.1016/j.vaccine.2006.09.061. Epub 2006 Oct 2.
• [22] Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children.EBioMedicine. 2015 Dec 2;3:93-99. doi: 10.1016/j.ebiom.2015.11.048. eCollection 2016 Jan.