Association of a bacteriophage with meningococcal disease in young adults

Abstract

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases.

Figure 1. Distribution of the integrated phage in disease isolates by age of patient.

(A) Comparison of the age distribution of meningococcal disease in the population studied. (B) Comparison of the age distribution of disease caused by MDA-positive (grey bars) and by MDA-negative (white bars) meningococci. Numbers of cases in each of the two groups are separately normalised to unity. (C) Relative proportions of disease in each of four age groups caused by MDA-positive or MDA-negative meningococci. The age groups were chosen in order to contain approximately equal numbers of meningococcal isolates. Two of these (the age bracket 0 to 2 years and 13 to 28 years) correspond to the periods of peak incidence of disease, respectively in infancy and in young adulthood.