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

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.

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.

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.

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.