Article Figures & Data
Figures
- FIG 1
Disposition of subjects (intent-to-treat population).
- FIG 2
Neisseria meningitidis serogroup B (NmB) carriage prevalence rates at each visit for both cohorts. NmB carriage was determined by seroagglutination, isolate PCR, and direct swab PCR assays at 3 visits and any visit for ninth-grade students (A) and university students (C) and by isolate whole-genome sequencing (WGS), isolate PCR, direct swab PCR, and live cell phenotypic assay (LCPA) for eleventh-grade/college entry students (B). *, P < 0.05. CIs were calculated using the exact method based on Clopper-Pearson (2-sided). The McNemar test using the exact method was used to compare the prevalence rates between PCR analyses and seroagglutination for each visit in ninth-grade/university students.
- FIG 3
Frequency of Neisseria meningitidis serogroup B (NmB) results by 3 diagnostic methods for both cohorts. The numbers of instances in which NmB was detected for subjects by seroagglutination, isolate PCR, direct swab PCR (ninth-grade and university students); by isolate whole-genome sequencing (WGS), isolate PCR, direct swab PCR, and live cell phenotypic assay (LCPA) (eleventh-grade/college entry students); and by multiple methods are shown as Venn diagrams for ninth-grade students (A), eleventh-grade/college entry students (B), and university students (C).
- FIG 4
Neisseria meningitidis serogroup B (NmB) and non-NmB carriage analyses for both cohorts. NmB isolates from all 3 visits (n = 45) (A) were characterized by whole-genome sequencing (WGS) to determine multilocus sequence typing (MLST)/clonal complex and factor H binding protein (fHBP) assignment. Results are presented for ninth-grade, eleventh-grade/college entry, and university students. Non-NmB isolates (B) from all 3 visits (n = 143) were characterized by PCR (serogroup assignment, except eleventh grade by WGS) and sequence analysis (fHBP assignment). NT, nontypeable; NG, nongroupable.
Tables
- TABLE 1
Summary of meningococcal carriage prevalence rates at each visit by isolate PCR (ITT population)g
Visit
(swab)Cohort Age group
(Ne)N. meningitidis serogroup detection from throat swab, n (%)a,b NmBc NmC NmY NmW Nongroupable NmE or
NmZAll
non-NmBdAll
meningococciVisit 1 1 9th grade (533) 4 (0.8) 2 (0.4) 8 (1.5) 4 (0.8) 16 (3.0) 3 (0.6) 33 (6.2) 37 (6.9) 11th gradef (363) 4 (1.1) 1 (0.3) 3 (0.8) 1 (0.3) 10 (2.8) 2 (0.6) 17 (4.7) 21 (5.8) 2 University (360) 20 (5.6) 3 (0.8) 5 (1.4) 8 (2.2) 35 (9.7) 16 (4.4) 67 (18.6) 87 (24.2) Visit 2 1 9th grade (417) 7 (1.7) 1 (0.2) 4 (1.0) 1 (0.2) 15 (3.6) 0 (0.0) 21 (5.0) 28 (6.7) 11th grade (363) 5 (1.4) 1 (0.3) 2 (0.6) 0 (0.0) 8 (2.2) 2 (0.6) 13 (3.6) 18 (5.0) 2 University (356) 16 (4.5) 3 (0.8) 3 (0.8) 6 (1.7) 31 (8.7) 9 (2.5) 52 (14.6) 68 (19.1) Visit 3 1 9th grade (526) 8 (1.5) 1 (0.2) 5 (1.0) 3 (0.6) 14 (2.7) 1 (0.2) 24 (4.6) 32 (6.1) College entry (356) 4 (1.1) 0 (0.0) 2 (0.6) 1 (0.3) 12 (3.4) 3 (0.8) 18 (5.1) 22 (6.2) 2 University (339) 17 (5.0) 4 (1.2) 6 (1.8) 7 (2.1) 27 (8.0) 8 (2.4) 52 (15.3) 69 (20.4) Any visit 1 9th grade (533) 11 (2.1) 2 (0.4) 9 (1.7) 5 (0.9) 19 (3.6) 3 (0.6) 39 (7.3) 49 (9.2) 11th grade/college
entry (363)6 (1.7) 1 (0.3) 4 (1.1) 1 (0.3) 17 (4.7) 3 (0.8) 26 (7.2) 32 (8.8) 2 University (360) 27 (7.5) 4 (1.1) 8 (2.2) 9 (2.5) 42 (11.7) 15 (4.2) 79 (21.9) 105 (29.1) ↵a n (%) is the number and percentage of subjects with positive meningococci carriage at that visit.
↵b No NmA or NmX isolates were detected.
↵c NmB PCR data were confirmed by WGS.
↵d All non-NmB meningococci: A, C, X, Y, W, nongroupable, Z, and E.
↵e N is number of subjects who had a culture performed at that visit.
↵f Eleventh-grade/college-entry students are the same (former) ninth-grade students.
↵g Abbreviations: ITT, intent-to-treat; Nm, Neisseria meningitidis; isolate PCR assay was performed by real-time PCR. Non-NmB meningococci include any sample in which the porA and/or ctrA gene(s) was detected but the group B capsule gene was not detected. Missing data were not imputed.
- TABLE 2
Carriage rates for nongroupable isolates at any visit
Method No. of subjects with positive non-NmB meningococcal carriage at any visit/no. ofsubjects with ≥1 culture performed at any visit (% [95% CIa]) by cohort: Ninth-grade students University students Seroagglutination 36/533 (6.8 [4.8, 9.2]) 79/360 (21.9 [17.8, 26.6]) Isolate PCR 21/533 (3.9 [2.5, 6.0]) 44/360 (12.2 [9.0, 16.1]) P valueb 0.001 <0.001 - TABLE 3
Microbiologic analyses of samples by cohort and time point (ITT population)c
Visit
(swab)Cohort Age group Analysis method, na Seroagglutination Isolate
PCRDirect
swab
PCRIsolate
WGSIsolate
LCPAMLST Visit 1 1 9th grade 36 36 469 11th grade 21 361 21 21 21 2 University 87 102 327 Visit 2 1 9th grade 28 28 339 11th grade 18 363 18 18 18 2 University 68 77 342 Visit 3 1 9th grade 33 34 451 College entry 22 356 22 22 22 2 University 35 39 338 Any visitb 1 9th grade 48 533 531 College entry 31 363 31 31 31 2 University 99 360 359 - TABLE 4
Definitions of meningococcal categories used in PCR analysesa
Category Isolate PCR Direct swab PCR WGS All meningococci Any sample in which the porA and/or ctrA gene(s) was detected Any sample in which the porA and/or ctrA gene(s) and/or the group B capsule gene was detected Any sample in which the porA and/or ctrA sequences were predicted to encode full-length gene product Grouped meningococci Any sample in which the porA and/or ctrA gene(s) and the relevant group capsule gene were detected Performed only for NmB Any sample in which the porA and/or ctrA sequences and all the required genes for synthesis and transport of the relevant capsule group were predicted to encode full-length gene products Nongroupable meningococci Any sample in which the porA and/or ctrA gene(s) was detected but no capsule gene was detected Not applicable Any sample in which the porA and ctrA sequences were predicted to encode full-length gene product and lacking any of the required genes for synthesis and transport of the relevant capsule group OR any sample in which the ctrA sequence is incomplete Non-NmB meningococci Not applicable Any sample in which the porA and/or ctrA gene(s) was detected but the group B capsule gene was not detected Not applicable Group B meningococci See “Grouped meningococci” above Any sample in which the group B capsule gene was detected See “Grouped meningococci” above ↵a Abbreviations: NmB, Neisseria meningitidis serogroup B; WGS, whole-genome sequencing.
