Experimental meningococcal infection in neonatal mice: differences in virulence between strains isolated from human cases and carriers.

Abstract

The lack of availability of a suitable animal model has limited understanding of the pathophysiology of meningococcal disease. We have utilized a neonatal mouse model in which atraumatic intranasal inoculation of meningococci results in nasopharyngeal colonization and ultimately bacteremia. Using this model, we compared the virulence of seven encapsulated meningococcal carrier strains with eight meningococcal strains which were isolated from cerebrospinal fluid or blood of patients (disease strains). Intraperitoneal (IP) iron dextran was given to some animals to enhance meningococcal virulence. After IP iron, carrier strains were still poorly invasive with rates of bacteremia ranging from 0 to 15% (mean = 3%), whereas disease-associated strains were significantly more invasive and caused bacteremia in 31-64% of animals (mean = 39%). Without iron injections, nasopharyngeal colonization rates were similar (36 versus 30%, P greater than 0.1) for case and carrier strains. IP iron dextran significantly enhanced rates of colonization and bacteremia caused by the disease strains only. We have, therefore, shown that the relative virulence of meningococcal strains for humans is maintained in this experimental model.