European Journal of Epidemiology

, Volume 20, Issue 7, pp 629–633 | Cite as

Applying a case-crossover study design to examine transient exposures in the transmission of N. meningitidis

  • R. Reintjes
  • H.  Kajueter
  • I.  Ehrhard
  • U. van Treeck
  • A.  Ammon
Infectious Diseases


Background: Meningococcal disease is a serious public health problem with a case fatality of about 10%. Recent acquisition of the bacteria is generally regarded as an important risk factor for developing the invasive disease. A case-crossover study to examine the effect of transient exposures on the acute outcome, which is the acquisition of Neisseria meningitidis, was undertaken. Methods: In the case-crossover design each case serves as its own matched control while case-times are compared to earlier time periods. Data from a longitudinal study was used for a case-crossover analysis. About 1910 students aged 14--19 were tested for meningococcal carriage and interviewed about potential risk factors. About 121 matched pairs of students who were non-carriers in the first survey and became carriers in the second were analysed. Mantel Haenszel Odds Ratios were calculated and a conditional logistic regression analysis was done. Results: Both bivariate and multivariate analysis showed a significant association between meningococcal carriage and the predicting variables rhinitis, visits to cinema, and travelling abroad. While the adjusted results for rhinitis (OR: 0.33; 95% CI: 0.13--0.82) and cinema visits (OR: 0.17; 95% CI: 0.05--0.65) indicate a protective association, travelling abroad (OR: 3.50; 95% CI: 1.45--8.34) turned out as a risk factor. Conclusions: Transient exposures that trigger the infection with N. meningitidis are generally difficult to study. This case-crossover study allows new insights in this process. For the interpretation of the results methodological issues and potential confounding (e.g., seasonal variation) need to be taken into account, especially while comparing the results with those from studies with traditional designs.

Key words

Case-crossover study Transient exposures Transmission of N. meningitidis 


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  1. 1.
    Robert Koch-Institut. Meningokokken-Erkrankungen; Jahresbericht 2002. Epidemiologisches Bulletin 2002; Nr. 33Google Scholar
  2. 2.
    Broome, CV 1986The carrier state: Neisseria meningitidisJ Antimicrob Chemoth182534Google Scholar
  3. 3.
    Conyn-van Spaendonck, MA, Reintjes, R, Spanjaard, L, Kregten, E, Kraaijeveld, AG, Jacobs, PH 1999Meningococcal carriage in relation to an outbreak of invasive disease due to Neisseria meningitis serogroup C in the NetherlandsJ Infection394248CrossRefGoogle Scholar
  4. 4.
    Cartwright K. Meningococcal disease. Cartwright K (ed), Chichester: John Wiley and Sons, 1995Google Scholar
  5. 5.
    Caugant, DA, Hoiby, EA, Magnus, P,  et al. 1994Asymptomatic carriage of Neisseria meningitidis in a randomly sampled populationJ Clin Microbiol32323330PubMedGoogle Scholar
  6. 6.
    Hauri, AM, Ehrhard, I, Frank, U,  et al. 2000Feb; Serogroup C meningococcal disease outbreak associated with discotheque attendance during carnivalEpidemiol Infect1246973CrossRefPubMedGoogle Scholar
  7. 7.
    Meier, CR, Jick, SS, Derby, LE, Vasilakis, C, Jick, H 1998Acute respiratory-tract infections and risk of first-time acute myocardial infarctionLancet35114671471CrossRefPubMedGoogle Scholar
  8. 8.
    Mittleman, MA, Maclure, M, Tofler, GH, Sherwood, JB, Goldberg, RJ, Muller, JE 1993Triggering of acute myocardial infarction by heavy physical exertion: protection against triggering by regular exertionNew Engl J Med32916771683CrossRefPubMedGoogle Scholar
  9. 9.
    Sorock, GS, Lombardi, DA, Gabel, CL, Smith, GS, Mittleman, MA 2001Case-crossover studies of occupational trauma: methodological caveatsInjury Prevention7i3842CrossRefPubMedGoogle Scholar
  10. 10.
    Dixon, KE 1997A comparison of case-crossover and case-control designs in a study of risk factors for hemorrhagic fever with renal syndromeEpidemiology8243246CrossRefPubMedGoogle Scholar
  11. 11.
    Rothman, KJ, Greenland, S 1998Modern Epidemiology2nd Ed.Lippincott-RavenPhiladelphiaGoogle Scholar
  12. 12.
    Robert Koch-Institut2000Zur Meningokokken-Trägerrate bei Jugendlichen in Nordrhein-Westfalen (NRW)Epidemiologisches Bull35281282Google Scholar
  13. 13.
    Maclure, M, Mittleman, MA 2000Should we use a case-crossover design?Annu Rev Public Health21193221CrossRefPubMedGoogle Scholar
  14. 14.
    Glitza IC. Longitudinalstudie zur Meningokokkenträgerrate von Jugendlichen in Nordrhein-Westfalen. Inauguraldissertation Ruprecht-Karls-Universität Heidelberg 2004Google Scholar
  15. 15.
    Cookson, ST, Corrales, JL, Lotero, JO, Regueira, M, Binsztein, N,  et al. 1998Disco fever: epidemic meningococcal disease in Northeastern Argentina associated with disco patronageJ Infect Dis178266269PubMedGoogle Scholar
  16. 16.
    Imrey, PB, Jackson, LA, Ludwinski, PH,  et al. 1996An outbreak of serogroup C meningococcal disease associated with campus bar patronageAm J Epidemiol143624630PubMedGoogle Scholar
  17. 17.
    Neal, KR, Nguyen-Van-Tam, JS, Jeffrey, N,  et al. 2000Changing carriage rate of Neisseria meningitidis among university students during first week of term: cross sectional studyBr Med J320846849Google Scholar
  18. 18.
    Simmons, G, Martin, D, Stewart, J, Jones, N, Calder, L, Bremner, D 2001Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New ZealandEur J Clin Microbiol Infect Dis20237242CrossRefPubMedGoogle Scholar
  19. 19.
    Stang, A, Joeckel, K 2004Appending epidemiological studies to conventional case-control studies (hybride case-control studies)Eur J Epidemiol19527532CrossRefPubMedGoogle Scholar
  20. 20.
    Ichhpujani, RL, Mohan, R, Grover, SS, Joshi, PR, Kumari, S 1990Nasopharyngeal carriage of Neisseria meningitidis in general population and meningococcal diseaseJ Commun Dis22264268PubMedGoogle Scholar
  21. 21.
    Suissa, S 1995The case-time-control designEpidemiology6248253PubMedGoogle Scholar
  22. 22.
    Greenland, S 1996Confounding and exposure trends in case-crossover and case-time-control designsEpidemiology7231239PubMedGoogle Scholar
  23. 23.
    Mittleman, MA, Maclure, M, Robins, JM 1995Control sampling strategies for case-crossover studies: an assessment of relative efficiencyAm J Epidemiol1429198PubMedGoogle Scholar
  24. 24.
    Rosenstein, NE, Perkins, BA, Stephens, DS, Popovic, T, Hughes, JM 2001Meningococcal DiseaseN Engl J Med34413781388CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • R. Reintjes
    • 1
    • 2
  • H.  Kajueter
    • 1
  • I.  Ehrhard
    • 3
    • 4
  • U. van Treeck
    • 2
  • A.  Ammon
    • 5
  1. 1.Hamburg University of Applied SciencesHamburgGermany
  2. 2.Institute of Public Health NorthRhine-WestphaliaGermany
  3. 3.University of HeidelbergGermany
  4. 4.Landesuntersuchungsanstalt für das Gesundheits- und Veterinärwesen SachsenDresdenGermany
  5. 5.Robert Koch-InstituteBerlinGermany

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