title: Meningococcal serogroup Y lpxL1 variants from South Africa are associated with clonal complex 23 among young adults.
abstract: OBJECTIVE
  To determine the genotypes of serogroup Y meningococcus (MenY), and to determine the prevalence of and identify factors associated with MenY lpxL1 variants.
  
  
  METHODS
  Isolates, collected from 2003 to 2007 through national surveillance for invasive meningococcal disease, were characterized by multilocus sequence typing and screened for interleukin-6 induction. LpxL1 genes were sequenced from low IL-6 inducers.
  
  
  RESULTS
  MenY represented 13% (n = 219/1702) of meningococcal disease. Clonal complex (cc) 175, ST-23/Cluster A3 (cc23), cc11 and cc167 accounted for 82% (176/214), 11% (24/214), 3% (6/214) and 3% (7/214) respectively. Low cytokine induction was evident in 15% (32/218). Cc23 isolates (24/24) had an lpxL1 mutation, while among the remaining isolates the proportion of lpxL1 variants was 4% (8/189, p < 0.001), and these were all cc175. Compared to wild type isolates, lpxL1 variants were associated with patients aged 5-14 years [unadjusted OR (95% CI): 4.3 (1.5-12)] or 15-24 years [unadjusted OR (95% CI): 9.1 (2.8-29)] compared to children <5 years; and were more likely have been isolated from CSF than blood [unadjusted OR (95% CI): 3.5 (1-11.9)]. On multivariable analysis, age remained significant [adjusted OR (95% CI), 5-14 years: 4.2 (1.5-12); 15-24 years: 8.9 (2.7-29)].
  
  
  CONCLUSIONS
  LpxL1 variants were associated with cc23 among young adults.
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Johannesburg, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: mignond@nicd.ac.za.
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Johannesburg, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Penny
authors.initials: P
authors.lastname: Crowther-Gibson
authors.affiliation: Department of Vaccinology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Hendrik-Jan
authors.initials: HJ
authors.lastname: Hamstra
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Center for Infection and Immunity, Amsterdam, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Schipper
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Johannesburg, South Africa.
authors.forename: Chivonne
authors.initials: C
authors.lastname: Moodley
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Department of Neurology, Academic Medical Center, Center for Infection and Immunity, Amsterdam, The Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.affiliation: Department of Vaccinology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Johannesburg, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Center for Infection and Immunity, Amsterdam, The Netherlands; Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology*; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D038581:Neisseria meningitidis, Serogroup Y / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D015850:Interleukin-6; D000217:Acyltransferases; C118473:LpxL protein, bacteria
keywords: Clonal complex 23; MLST; Neisseria meningitidis; Serogroup Y; South Africa; lpxL