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Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer

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ABSTRACT

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.

No MeSH data available.


Neighbor-Net diagram depicting genetic relationships of ST-6697 isolates generated from an allele-by-allele comparison of 1,505 core meningococcal genes. Carried strains recovered from throat swabs volunteered by the family members in December 2013 (n = 8, triangles) and case isolates B and H (circles). Also included is a single example of an ST-6697 meningococcus from a historical IMD case with an address in one of the towns where the family members reside (town B), isolated 13 months prior to the start of the outbreak (green bar).
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Figure 4: Neighbor-Net diagram depicting genetic relationships of ST-6697 isolates generated from an allele-by-allele comparison of 1,505 core meningococcal genes. Carried strains recovered from throat swabs volunteered by the family members in December 2013 (n = 8, triangles) and case isolates B and H (circles). Also included is a single example of an ST-6697 meningococcus from a historical IMD case with an address in one of the towns where the family members reside (town B), isolated 13 months prior to the start of the outbreak (green bar).

Mentions: The relatedness of 11 ST6697 isolates, based on an allele-by-allele comparison of the core N. meningitidis genome (1,605 loci), was determined (Fig. 4). This included eight carriage isolates (December 2013), outbreak case B and H isolates (November 2010 and 2013, respectively), and one ST6697 isolate from an individual from the general population living in town B and predating the outbreak (February 2009). The latter isolate differed from the case B isolate at 41/1,605 loci, and both isolates were more related to each other than to the other meningococcal isolates. Carriage isolate M1 showed the greatest similarity to the most recent invasive isolate, case H, differing at 13/1,605 core loci (0.8%), representing 49 nucleotide differences. This very likely represents direct transmission among family members of the same strain that caused invasive disease 1 month earlier. Isolates M2, M13, and M34 represent three variants of another meroclone, grouped very closely to each other but not to any other isolates, again representing direct person-to-person transmission.


Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer
Neighbor-Net diagram depicting genetic relationships of ST-6697 isolates generated from an allele-by-allele comparison of 1,505 core meningococcal genes. Carried strains recovered from throat swabs volunteered by the family members in December 2013 (n = 8, triangles) and case isolates B and H (circles). Also included is a single example of an ST-6697 meningococcus from a historical IMD case with an address in one of the towns where the family members reside (town B), isolated 13 months prior to the start of the outbreak (green bar).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121376&req=5

Figure 4: Neighbor-Net diagram depicting genetic relationships of ST-6697 isolates generated from an allele-by-allele comparison of 1,505 core meningococcal genes. Carried strains recovered from throat swabs volunteered by the family members in December 2013 (n = 8, triangles) and case isolates B and H (circles). Also included is a single example of an ST-6697 meningococcus from a historical IMD case with an address in one of the towns where the family members reside (town B), isolated 13 months prior to the start of the outbreak (green bar).
Mentions: The relatedness of 11 ST6697 isolates, based on an allele-by-allele comparison of the core N. meningitidis genome (1,605 loci), was determined (Fig. 4). This included eight carriage isolates (December 2013), outbreak case B and H isolates (November 2010 and 2013, respectively), and one ST6697 isolate from an individual from the general population living in town B and predating the outbreak (February 2009). The latter isolate differed from the case B isolate at 41/1,605 loci, and both isolates were more related to each other than to the other meningococcal isolates. Carriage isolate M1 showed the greatest similarity to the most recent invasive isolate, case H, differing at 13/1,605 core loci (0.8%), representing 49 nucleotide differences. This very likely represents direct transmission among family members of the same strain that caused invasive disease 1 month earlier. Isolates M2, M13, and M34 represent three variants of another meroclone, grouped very closely to each other but not to any other isolates, again representing direct person-to-person transmission.

View Article: PubMed Central - PubMed

ABSTRACT

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.

No MeSH data available.