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We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings.In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9;n = 132), or a control vaccine (meningococcus C vaccine;n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility.Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively;P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively;P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively;P < 0.001) and their younger siblings (19% vs. 13%, respectively;P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to ≥1, ≥2 and ≥3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls.The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.