Diversity in pathogenicity can cause outbreaks of meningococcal disease

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Abstract
Neisseria meningitidis, the meningococcus, is a major cause of bacterial meningitis and septicemia worldwide. Infection in most cases leads to asymptomatic carriage and only rarely to disease. Meningococcal disease often occurs in outbreaks, which are both sporadic and highly unpredictable. The occurrence of disease outbreaks in a host population in which the etiological agent is widely carried is not well understood. A potential explanation lies in the fact that meningococci are diverse with respect to disease-causing potential. We formulated a stochastic mathematical model to investigate whether diversity of the bacterial population is related to outbreaks of meningococcal disease. In the model, strains that occasionally cause the disease appear repeatedly in a population dominated by a nonpathogenic strain. When the pathogenicity, i.e., the disease-causing potential, of the pathogenic lineage was low, the model shows distinct outbreaks, the size distribution of the outbreaks follows a power law, and the ratio of the variance to the mean number of cases is high. Analysis of notification data of meningococcal disease showed that the ratio of the variance to the mean was significantly higher for meningococcal diseases than for other bacterial invasive diseases. This result lends support to the hypothesis that outbreaks of meningococcal disease are caused by diversity in the pathogenicity of meningococcal strains.