Experimental meningococcal infection in neonatal animals: models for mucosal invasiveness

Abstract

A more complete understanding of meningococcal disease has been hampered by lack of an appropriate animal model. We subjected 5-day-old guinea pigs, rats, and mice to intranasal challenge with meningococci and we measured rates of bacteremia as a marker of mucosal invasion. After a single intranasal instillation of 107 serotype 2 meningococci, positive blood cultures were found in 0% of guinea pigs, 16% of rats, and 39% of mice, and so mice were used for further studies. Death occurred in 4% of mice and was associated with a purulent leptomeningitis and ventriculitis. Forty percent of mice had nasopharyngeal colonization which increased to 65% with repeated injections. Carrier strains were avirulent, a nonserotype 2 disease strain had low invasiveness, and serotype 2 strains were most virulent. Iron dextran increased rates of bacteremia after challenge with serotype 2 strains. Adult animals were not susceptible to bacteremia after intranasal challenge. The neonatal mouse model fulfills most of the criteria for an appropriate experimental model of meningococcal disease.