Toward a Global Genomic Epidemiology of Meningococcal Disease

Retchless, Adam C.; Fox, LeAnne M.; Maiden, Martin C. J.; Smith, Vincent C.; Harrison, Lee H.; Glennie, Linda; Harrison, Odile; Wang, Xin

doi:10.1093/infdis/jiz279

Cited by 17 publications

(12 citation statements)

References 45 publications

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“…In the longer term, whole genome sequencing (WGS) will become more routinely employed in the diagnosis of infectious diseases, including meningitis [74]. Ultimately, this will likely include the development of non-culture-based methods that directly sequence pathogen genomes from clinical specimens.…”

Section: Outstanding Questionsmentioning

confidence: 99%

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review

et al. 2021

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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.

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Section: Outstanding Questionsmentioning

confidence: 99%

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review

et al. 2021

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“…understand Nm transmission, investigate the impact of genomic variation on the clinical outcome of disease (11), and monitor genomic epidemiology (12). Specifically, whole genome sequencing (WGS) is increasingly used for molecular typing of Nm, allowing allelic or SNP-based whole genome analyses to improve typing resolution (13,14).…”

Section: Downloaded Frommentioning

confidence: 99%

Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation

Itsko

Retchless

Joseph³

et al. 2020

J Clin Microbiol

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Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole genome amplification (SWGA), an isothermal multiple displacement amplification-based method, to efficiently enrich, sequence and de novo assemble Nm DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of Nm reads by 2-3 orders of magnitude enabling identification of at least 90% of the 1605 Nm core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial load were processed by SWGA before sequencing and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the Nm pathogen, therefore enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rate. SWGA produces enough reads for phylogenetic and allelic analysis with a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.

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“…In 2017, cases of NmC disease also occurred in other countries, both within (Benin, Burkina Faso, Mali) and outside (Liberia) the meningitis belt [17, 31–33]. MenAfriNet-supported investigations have documented the largest global outbreak of NmC in Niger, characterized the molecular ST of NmC strains from outbreaks in Mali and Burkina Faso, and documented substantial burdens of W and X in Togo and Chad, respectively [13, 14, 16, 18, 34]. In 2015 and 2017, a committee of experts was convened by WHO to review the emergence of NmC [35, 36].…”

Section: Ongoing Developments In Meningococcal Disease and Role Of Mementioning

confidence: 99%

“…The emergence of a unique epidemic-prone NmC strain, continued epidemic threat of NmW and NmX, ongoing endemic disease with focal outbreaks of pneumococcal meningitis, and continued occurrence of serotype 1 pneumococcal disease after implementation of infant PCV immunization underscore the value of high-quality meningitis surveillance, including strong laboratory capacity for rapid detection and serogrouping/serotyping of vaccine-preventable bacterial meningitis pathogens, and genome sequencing to monitor the molecular evolution of meningococcal and pneumococcal strains [20, 34, 42].…”

Section: Ongoing Developments In Meningococcal Disease and Role Of Mementioning

confidence: 99%

“…Although WGS has been implemented in many public health laboratories in high-income countries for surveillance and outbreak investigations, resource-limited countries face challenges related to infrastructure (ie, power fluctuations) and human resources (eg, limited opportunities for training in informatics analysis) when considering this technology. Further innovations in sequencing technology should make WGS more accessible to public health laboratories in resource-limited settings [34]. Until these barriers are bridged, sub-Saharan meningitis belt countries are encouraged to collaborate with global and regional reference laboratories equipped to perform WGS, such as WHO Collaborating Centers and Regional Reference Laboratories [50, 52].…”

Section: The Futurementioning

confidence: 99%

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Future Directions for Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Sub-Saharan Africa

Novak

Ronveaux²,

Bita

et al. 2019

The Journal of Infectious Diseases

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In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of “Defeating Meningitis by 2030,” MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa.

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Toward a Global Genomic Epidemiology of Meningococcal Disease

Cited by 17 publications

References 45 publications

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review

Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation

Future Directions for Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Sub-Saharan Africa

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