A RHESUS MACAQUE MODEL OF STREPTOCOCCUS PNEUMONIAE CARRIAGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pneumococcal infection causes an estimated 40,000 deaths annually in the US. Colonization of the nasopharynx by S. pneumoniae always precedes pneumococcal disease. Therefore, elucidation of procedures to prevent or eradicate nasopharyngeal (NP) carriage would help diminish the incidence of both pneumonia and invasive disease. We thus endeavored to develop a rhesus monkey model of S. pneumoniae carriage, to complement and improve upon the existing rodent models, with an animal whose NP anatomy and epithelial lining is more akin to the human. We first surveyed the nasopharynx of infant rhesus macaques from the Center's breeding colony, in search of animals that were natural carriers. A total of 158 rhesus of a median age of 1.23 years (range 0.59  1.99) were surveyed. No S. pneumoniae colonies were isolated from any of the animals. Thus rhesus are not likely natural carriers of S. pneumoniae. Second, we attempted to induce carriage experimentally in infants (n = 8), by NP instillation of a human S. pneumoniae strain (19F). This was done both in antibiotic pre-treated and untreated animals. We also searched for pneumonia and disseminated infection secondary to colonization, and whether these forms of infection could be facilitated by splenectomy. The rate of NP colonization remained at 100% for 2 weeks post-instillation (PI), and above 60% for 7 weeks. It then oscillated around 30% until week 14, when the study ended; it did not appear to be affected by antibiotic pre-treatment. Four of the animals were splenectomized between weeks 5 and 6 PI. There was no invasive infection or disease in any of the animals, splenectomized or eusplenic, at any time. Blood and BAL cultures were negative throughout, and X-rays, CBC, and serum chemistry analyses were normal at all times. We concluded that the rhesus monkey is a suitable model to study pneumococcal colonization. However, the transition to invasive disease may not be fostered by splenectomy in this model.