We analyzed >70 recent data sets to compare the serogroups causing invasive pneumococcal disease (IPD) with those represented in conjugate vaccine formulations. Five to 8 and 10-11 serogroups comprise at least 75% of pneumococcal isolates from young children and older children/adults, respectively, in each geographic region. Serogroups in the 7-valent formulation (4, 6, 9, 14, 18, 19, and 23) cause 70%-88% of IPD in young children in the United States and Canada, Oceania, Africa, and Europe, and <65% in Latin America and Asia. Serogroups in the 9-valent formulation (7-valent+1, 5) cause 80%-90% of IPD in each region except Asia (66%). Serogroup 1 accounts for >6% of IPD in each region, including Europe, except the United States and Canada and Oceania. In contrast, several serogroups not found in 7-, 9-, and 11-valent conjugate formulations are significant causes of disease in older children/adults. Nevertheless, each conjugate formulation could prevent a substantial IPD burden in each region and age group.
To assess whether certain serogroups of Streptococcus pneumoniae are preferentially associated with specific disease manifestations, we analyzed all recent pneumococcal disease studies and assessed the relative frequency of isolation of each serogroup by clinical site (as a proxy for different disease states). In all age groups, serogroups 1 and 14 were more often isolated from blood, and serogroups 6, 10, and 23 were more often isolated from cerebrospinal fluid (CSF); in young children, serogroups 3, 19, and 23 were more often isolated from middle ear fluid (MEF). Serogroups represented in conjugate vaccines were isolated slightly less frequently from CSF than from blood or MEF. Nonetheless, serogroups in the 9-valent conjugate vaccine formulation still comprised approximately 75% of pneumococcal isolates from the CSF of young children in Europe and in the United States and Canada. These analyses indicate that pneumococcal conjugate vaccines could potentially prevent a substantial proportion of episodes of bacteremic disease, pneumonia, meningitis, and otitis media, especially in young children.
Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.
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