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Correspondence

Rapid Serogroup Switching in Neisseria meningitidis

N Engl J Med 2000; 342:219-220January 20, 2000

Article

To the Editor:

In Neisseria meningitidis, the horizontal transfer of siaD genes encoding polysialyltransferases has been shown to result in capsular serogroup switching in vitro.1 The presence of closely related clones with different serogroups suggests that serogroup switching also occurs in vivo.2,3 However, the time course of the transfer of siaD genes in humans is unknown.

We describe a case of unexpectedly rapid serogroup switching in virulent meningococci. A 16-year-old girl died of fulminant serogroup B meningococcal septicemia. Examination of nasopharyngeal swabs from close contacts revealed massive colonization with serogroup C meningococci in the girl's boyfriend. Isolates from the girl and her boyfriend were identical with respect to the typing of porin antigens (15:P1.16) and the sequence type (ST 32).4 We used pulsed-field gel electrophoresis and the restriction endonuclease SpeI to demonstrate the direct clonal descendence of the strains.5 The two strains yielded almost identical restriction fragments. However, the serogroup C strain had one unique band of approximately 210 kb, which hybridized to a probe specific to the serogroup C siaD gene. In the serogroup B strain, this fragment was cleaved into two fragments of approximately 160 kb and 50 kb, which hybridized to a serogroup B siaD probe. To show that these differences were due to siaD exchange, the siaD genes of both strains were amplified by the polymerase chain reaction (PCR) and digested with SpeI. As with the result obtained by pulsed-field gel electrophoresis, the PCR product of the siaD gene in the serogroup B strain was cleaved by SpeI, whereas the PCR product of the siaD gene in the serogroup C strain was not (Figure 1Figure 1Genomic Organization of SpeI Restriction Fragments Containing Capsule-Synthesis Genes in Meningococcal Isolates from a 16-Year-Old Girl (Index Strain) and Her Boyfriend (Contact Strain).).

In view of the fact that an outbreak of meningococcal disease follows transmission of the meningococcus within only a few days, our report illustrates the extraordinary speed with which meningococci switch capsular serogroups. In the case we describe, the serogroup changed as a result of the transfer of serogroup-specific genes during the short period of transmission of the disease isolate. The rapidity of the serogroup switching arouses concern about the induction of herd immunity against single serogroups by vaccination programs in which capsular antigens (e.g., serogroup C polysaccharides) are used. Without lowering the incidence of meningococcal disease in the long run, such programs may rapidly increase the incidence of serogroup B meningococcal disease, for which no vaccine is available.

Ulrich Vogel, M.D.
Heike Claus, B.Sc.
Matthias Frosch, M.D.
Universität Würzburg, 97080 Würzburg, Germany

5 References
  1. 1

    Frosch M, Meyer TF. Transformation-mediated exchange of virulence determinants by co-cultivation of pathogenic Neisseriae. FEMS Microbiol Lett 1992;79:345-349
    Medline

  2. 2

    Swartley JS, Marfin AA, Edupuganti S, et al. Capsule switching of Neisseria meningitidis. Proc Natl Acad Sci U S A 1997;94:271-276
    CrossRef | Web of Science | Medline

  3. 3

    Kertesz DA, Coulthart MB, Ryan JA, Johnson WM, Ashton FE. Serogroup B, electrophoretic type 15 Neisseria meningitidis in Canada. J Infect Dis 1998;177:1754-1757
    CrossRef | Web of Science | Medline

  4. 4

    Maiden MC, Bygraves JA, Feil E, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 1998;95:3140-3145
    CrossRef | Web of Science | Medline

  5. 5

    Vogel U, Morelli G, Zurth K, et al. Necessity of molecular techniques to distinguish between Neisseria meningitidis strains isolated from patients with meningococcal disease and from their healthy contacts. J Clin Microbiol 1998;36:2465-2470[Erratum, J Clin Microbiol 1999;37:882.]
    Web of Science | Medline

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  1. 1

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  2. 2

    H. ZHOU, Y. GAO, L. XU, M. LI, Q. LI, Y. LI, X. LIANG, H. LUO, B. KAN, J. XU, Z. SHAO. (2011) Distribution of serogroups and sequence types in disease-associated and carrier strains of Neisseria meningitidis isolated in China between 2003 and 2008. Epidemiology and Infection1-8
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  3. 3

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  4. 4

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  5. 5

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  6. 6

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  7. 7

    Caroline L Trotter, Martin CJ Maiden. (2009) Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programs. Expert Review of Vaccines 8:7, 851-861
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  8. 8

    Lee H. Harrison, Caroline L. Trotter, Mary E. Ramsay. (2009) Global epidemiology of meningococcal disease. Vaccine 27, B51-B63
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  9. 9

    Dominique A. Caugant. (2008) Genetics and evolution of Neisseria meningitidis: Importance for the epidemiology of meningococcal disease. Infection, Genetics and Evolution 8:5, 558-565
    CrossRef

  10. 10

    J. E. Russell, R. Urwin, S. J. Gray, A. J. Fox, I. M. Feavers, M. C. J. Maiden. (2008) Molecular epidemiology of meningococcal disease in England and Wales 1975-1995, before the introduction of serogroup C conjugate vaccines. Microbiology 154:4, 1170-1177
    CrossRef

  11. 11

    T. Davidsen, M. Koomey, T. Tønjum. (2007) Microbial genome dynamics in CNS pathogenesis. Neuroscience 145:4, 1375-1387
    CrossRef

  12. 12

    Judith E Mueller, Raymond Borrow, Bradford D Gessner. (2006) Meningococcal serogroup W135 in the African meningitis belt: epidemiology, immunity and vaccines. Expert Review of Vaccines 5:3, 319-336
    CrossRef

  13. 13

    Marcelo Lancellotti, Annie Guiyoule, Corinne Ruckly, Eva Hong, Jean-Michel Alonso, Muhamed-Kheir Taha. (2006) Conserved virulence of C to B capsule switched Neisseria meningitidis clinical isolates belonging to ET-37/ST-11 clonal complex. Microbes and Infection 8:1, 191-196
    CrossRef

  14. 14

    Jens U R??ggeberg, Andrew J Pollard. (2004) Meningococcal Vaccines. Pediatric Drugs 6:4, 251-266
    CrossRef

  15. 15

    Wasim Maziak. (2002) Asthma and the exposure–disease tenet. Journal of Clinical Epidemiology 55:8, 737-740
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  16. 16

    Luis Jódar, Ian M Feavers, David Salisbury, Dan M Granoff. (2002) Development of vaccines against meningococcal disease. The Lancet 359:9316, 1499-1508
    CrossRef

  17. 17

    Sarah L. Morley, Andrew J. Pollard. (2001) Vaccine prevention of meningococcal disease, coming soon?. Vaccine 20:5-6, 666-687
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  18. 18

    M. A. Diggle, G. F. S. Edwards, S. C. Clarke. (2001) Developments in the diagnosis of meningococcal disease and the characterization of Neisseria meningitidis. Reviews in Medical Microbiology 12:4, 211-217
    CrossRef

  19. 19

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