Genotypic characterization and genome comparison reveal insights into potential vaccine coverage and genealogy of Neisseria meningitidis in military camps in Vietnam

Abstract

Background Neisseria meningitidis remains the main cause of sporadic meningitis and sepsis in military camps in Vietnam. Yet, very limited molecular data of their genotypic and epidemiological characteristics are available from Vietnam, and particularly the military environment. Whole genome sequencing (WGS) has proven useful for meningococcal disease surveillance and guiding preventative vaccination programs. Previously, we characterized key genetic and epidemiological features of an invasive N. meningitidis B isolate from a military unit in Vietnam. Here, we extend these findings by sequencing two additional invasive N. meningitidis B isolated from cerebrospinal fluid (CSF) of two meningitis cases at another military unit and compared their genomic sequences and features. We also report the sequence types and antigenic profiles of 25 historical and more recently emerged N. meningitidis isolates from these units and other units in proximity. Methods Strains were sequenced using the Illumina HiSeq platform, de novo assembled and annotated. Genomes were compared within and between military units, as well as against the global N. meningitidis collection and other isolates from the Southeast Asia region using PubMLST. Variations at the nucleotide level were determined, and phylogenetic relationships were estimated. Antigenic genotypes and vaccine coverage were analyzed using gMATS and PubMLST. Susceptibility of isolates against commonly used antibiotic agents was examined using E-test. Results Genome comparison revealed a high level of similarity among isolates both within and between units. All isolates showed resistance to chloramphenicol and carried identical catP gene with other Southeast Asian isolates, suggesting a common lineage. Their antigenic genotypes predicted no coverage by either Bexsero®or Trumenba®, and nucleotide variation analysis revealed diverse new, unassigned alleles at multiple virulence loci of all strains. Groups of singleton and unique novel sequence types extending beyond individual camps were found from epidemiological data of 25 other isolates. Our results add to the sparse published molecular data of N. meningitidis in the military units in Vietnam, highlight their diversity, distinct genetic features and antibiotic resistance pattern, and emphasize the need for further studies on the molecular characteristics of N. meningitidis in Vietnam.

Review of the epidemiology, diagnosis and management of invasive meningococcal disease in Vietnam

“…Pediatric populations were included in five studies. 13–17 Seven studies 12–16 , 18 , 19 reported epidemiologic outcomes ( Table 1 ) and information was identified on annual meningococcal meningitis case numbers from the Vietnam Medical Association. 20 Six studies 12 , 16 − 19 , 21 reported antibiotic susceptibility outcomes ( Table 2 ).…”

“… 15 Additional data on IMD serogroups were reported in three retrospective analyses of isolates from cases and/or carriers. 16 , 18 , 19 …”

“…From the three retrospective studies providing data on serogroups, the majority of IMD cases tested were serogroup B IMD (100% of five military population cases in 2008–2017, 18 100% of 11 hospitalized cases in 1987–1996 16 and 94% of 50 cases in South Vietnam in 1980–2019 vs. 6% serogroup C cases). 19 Serogroup B was also predominant among carriers, (i.e., 73.9% of 23 military population carriers tested vs. 26.1% with serogroup C 18 , and 56% of 59 carrier isolates tested vs. 21% for serogroup C 19 ).…”

“…Antibiotic susceptibility data ( Table 2 ) were reported in one prospective surveillance study, 12 three retrospective isolate analysis studies, 16 , 18 , 19 a retrospective case study 21 and a randomized controlled antibiotic trial. 17 …”

“…From studies in a military population; there were two IMD cases (from 8 isolates tested) with ceftriaxone resistance, the first line treatment for this population; 12 and two IMD cases (from 5 cases tested) with chloramphenicol resistance and reduced susceptibility to ampicillin. 18 Another drug-resistant isolate from a soldier hospitalized in 2014 with signs of sepsis and meningitis also had considerable resistance to chloramphenicol (minimal inhibitory concentration [MIC] 256 µg/ml) and reduced susceptibility to ampicillin and rifampicin. 21 …”