Enhancing Meningococcal Genomic Surveillance in the Meningitis Belt Using High-Resolution Culture-Free Whole-Genome Sequencing

Abstract

Rollout of meningococcal serogroup A conjugate vaccine in Africa started in 2010, aiming to eliminate meningitis outbreaks, in meningitis belt countries. Since then, studies have been conducted, primarily using isolates, to assess the vaccine impact on the distribution of meningococcal strains in the region. Here, we implemented an innovative, culture-free whole-genome sequencing approach on almost 400 clinical specimens collected between 2017 and 2019 from meningococcal meningitis cases in 6 African countries. About 50% of specimens provided high-quality whole-genome sequence data for comprehensive molecular profiling of the meningococcal pathogen. Three major clonal complexes were identified: CC11 associated with serogroup W, CC181 associated with serogroup X, and CC10217 associated with serogroup C, which continues to rise as a predominant clonal complex in the region. Genomic surveillance for meningococcal meningitis can be significantly improved using culture-free methods to increase data representativeness and monitor changes in epidemiological landscape, especially for countries with low culture rate.

Keywords: Neisseria meningitidis; culture-free whole-genome sequencing; meningococcal meningitis surveillance; selective whole-genome amplification; targeted sequencing.

Figure 1.

Distribution of meningococcal strains in meningitis belt countries. A, Major clonal complexes found among all sequenced clinical specimens (n = 233) and isolates (n = 109) by year. The additional clinical specimen belongs to CC41 and as a minor representative is not included in the panel. B, All unique sequence types according to pubMLST database [16] (black font, major [> 90%] sequence type; white font, minor [<10%] sequence type) found within each clonal complex in fully typed clinical specimens (n = 193) and isolates (n = 109) by country. The number of specimens found within each clonal, annual, geographic group is designated as n = number of clinical specimens/number of isolates.

Figure 2.

CC11 phylogenetic tree: Major clades/subclades are labeled with the countries and highlighted with corresponding colors. Specimens collected for the current (2017–2019) study are capped with squares for clinicals or circles for isolates. Uncapped specimens are from the previous study (2011–2016). The tree scale is in units of average substitutions per site along that length of the branch. Abbreviations: BF, Burkina Faso; CAR, Central African Republic.

Figure 3.

Phylogenesis of CC181 (A) and its plausible paths of expansion in meningitis belt countries (B). Major clades/subclades are labeled with the countries and corresponding years of strains identification. Specimens collected for the current (2017–2019) study are capped with squares for clinicals or circles for isolates. Uncapped specimens are from the previous study (2011–2016). The tree scale is in units of average substitutions per site along that length of the branch. Abbreviation: BF, Burkina Faso.

Figure 4.

CC10217 phylogenetic tree. Major clades/subclades are labeled with the countries and highlighted with corresponding colors. Specimens collected for the current (2017–2019) study are capped with squares for clinicals or circles for isolates. Uncapped specimens are from the previous study (2011–2016). The tree scale is in units of average substitutions per site along that length of the branch. Abbreviation: BF, Burkina Faso.