Molecular Diagnostic Assays for the Detection of Common Bacterial Meningitis Pathogens: A Narrative Review

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2021 Mar 15

PMID 33721818

Citations 10

Authors

Kanny Diallo

Vitalis F Feteh

Lilian Ibe

Martin Antonio

Dominique A Caugant

Mignon du Plessis

Ala-Eddine Deghmane

Ian M Feavers

Katya Fernandez

LeAnne M Fox

Charlene M C Rodrigues

Olivier Ronveaux

Muhamed-Kheir Taha

Xin Wang

Angela B Brueggemann

Martin C J Maiden

Odile B Harrison

Affiliations

Soon will be listed here.

Abstract

Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.

Citing Articles

Performance Comparison of Two In-House PCR Methods for Detecting in Asymptomatic Carriers and Antimicrobial Resistance Profiling.

Atimew M, Yidenekachew M, Yimer M, Alemu A, Hailu Alemayehu D, Wondimagegn T Diagnostics (Basel). 2025; 15(5).

PMID: 40075884 PMC: 11899361. DOI: 10.3390/diagnostics15050637.

Enhanced pathogen identification among patients with clinically suspected meningitis.

Moleleki M, Nel P, Matukane S, Cloete S, Abrahams Z, Wolter N S Afr J Infect Dis. 2025; 39(1):688.

PMID: 39822283 PMC: 11736564. DOI: 10.4102/sajid.v39i1.688.

Invasive Infections in Children in Vaccine Era: Phenotypic and Genotypic Characterization Tunis, Tunisia.

Chelbi Y, Meftah K, Deghmane A, Mhimdi S, Aloui F, Bouafsoun A Microorganisms. 2025; 12(12.

PMID: 39770868 PMC: 11728474. DOI: 10.3390/microorganisms12122666.

Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections.

Olie S, Andersen C, van de Beek D, Brouwer M Clin Microbiol Rev. 2024; 37(4):e0002124.

PMID: 39404267 PMC: 11629637. DOI: 10.1128/cmr.00021-24.

Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.

Shi Y, Tan Q, Gong T, Li Q, Zhu Y, Duan X Mikrochim Acta. 2024; 191(5):271.

PMID: 38632191 DOI: 10.1007/s00604-024-06309-0.

References

Ladhani S, Giuliani M, Biolchi A, Pizza M, Beebeejaun K, Lucidarme J . Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England. Emerg Infect Dis. 2016; 22(2):309-11. PMC: 4734511. DOI: 10.3201/eid2202.150369. View

DInzeo T, Menchinelli G, De Angelis G, Fiori B, Liotti F, Morandotti G . Implementation of the eazyplex CSF direct panel assay for rapid laboratory diagnosis of bacterial meningitis: 32-month experience at a tertiary care university hospital. Eur J Clin Microbiol Infect Dis. 2020; 39(10):1845-1853. DOI: 10.1007/s10096-020-03909-5. View

Deghmane A, Hong E, Chehboub S, Terrade A, Falguieres M, Sort M . High diversity of invasive Haemophilus influenzae isolates in France and the emergence of resistance to third generation cephalosporins by alteration of ftsI gene. J Infect. 2019; 79(1):7-14. DOI: 10.1016/j.jinf.2019.05.007. View

van de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek A . ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect. 2016; 22 Suppl 3:S37-62. DOI: 10.1016/j.cmi.2016.01.007. View

Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N . Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000; 28(12):E63. PMC: 102748. DOI: 10.1093/nar/28.12.e63. View

Carvalho M, Tondella M, McCaustland K, Weidlich L, McGee L, Mayer L . Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol. 2007; 45(8):2460-6. PMC: 1951257. DOI: 10.1128/JCM.02498-06. View

Retchless A, Fox L, Maiden M, Smith V, Harrison L, Glennie L . Toward a Global Genomic Epidemiology of Meningococcal Disease. J Infect Dis. 2019; 220(220 Suppl 4):S266-S273. DOI: 10.1093/infdis/jiz279. View

Magomani V, Wolter N, Tempia S, du Plessis M, de Gouveia L, von Gottberg A . Challenges of using molecular serotyping for surveillance of pneumococcal disease. J Clin Microbiol. 2014; 52(9):3271-6. PMC: 4313149. DOI: 10.1128/JCM.01061-14. View

Alderson M . Status of research and development of pediatric vaccines for Streptococcus pneumoniae. Vaccine. 2016; 34(26):2959-2961. PMC: 4906266. DOI: 10.1016/j.vaccine.2016.03.107. View

10.

Lam T, Elias J, Frosch M, Vogel U, Claus H . New diagnostic PCR for Haemophilus influenzae serotype e based on the cap locus of strain ATCC 8142. Int J Med Microbiol. 2010; 301(2):176-9. DOI: 10.1016/j.ijmm.2010.07.004. View

11.

Chang A, Adlowitz D, Yellamatty E, Pichichero M . Haemophilus influenzae outer membrane protein P6 molecular characterization may not differentiate all strains of H. Influenzae from H. haemolyticus. J Clin Microbiol. 2010; 48(10):3756-7. PMC: 2953139. DOI: 10.1128/JCM.01255-10. View

12.

Dube F, van Mens S, Robberts L, Wolter N, Nicol P, Mafofo J . Comparison of a Real-Time Multiplex PCR and Sequetyping Assay for Pneumococcal Serotyping. PLoS One. 2015; 10(9):e0137349. PMC: 4559314. DOI: 10.1371/journal.pone.0137349. View

13.

Bruce M, Deeks S, Zulz T, Navarro C, Palacios C, Case C . Epidemiology of Haemophilus influenzae serotype a, North American Arctic, 2000-2005. Emerg Infect Dis. 2008; 14(1):48-55. PMC: 2600153. DOI: 10.3201/eid1401.070822. View

14.

Zhang X, Guo L, Liu L, Shen A, Feng W, Huang W . The diagnostic value of metagenomic next-generation sequencing for identifying Streptococcus pneumoniae in paediatric bacterial meningitis. BMC Infect Dis. 2019; 19(1):495. PMC: 6549306. DOI: 10.1186/s12879-019-4132-y. View

15.

Booy R, Moxon E . Immunisation of infants against Haemophilus influenzae type b in the UK. Arch Dis Child. 1991; 66(10):1251-4. PMC: 1793483. DOI: 10.1136/adc.66.10.1251. View

16.

Hammerschmidt S, Muller A, Sillmann H, Muhlenhoff M, Borrow R, Fox A . Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease. Mol Microbiol. 1996; 20(6):1211-20. DOI: 10.1111/j.1365-2958.1996.tb02641.x. View

17.

Rodrigues C, Maiden M . A world without bacterial meningitis: how genomic epidemiology can inform vaccination strategy. F1000Res. 2018; 7:401. PMC: 5871810. DOI: 10.12688/f1000research.13793.1. View

18.

Favaro M, Savini V, Favalli C, Fontana C . A multi-target real-time PCR assay for rapid identification of meningitis-associated microorganisms. Mol Biotechnol. 2012; 53(1):74-9. DOI: 10.1007/s12033-012-9534-7. View

19.

Maiden M . The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1623):20120147. PMC: 3720045. DOI: 10.1098/rstb.2012.0147. View

20.

Higgins O, Smith T . Loop-Primer Endonuclease Cleavage-Loop-Mediated Isothermal Amplification Technology for Multiplex Pathogen Detection and Single-Nucleotide Polymorphism Identification. J Mol Diagn. 2020; 22(5):640-651. DOI: 10.1016/j.jmoldx.2020.02.002. View