Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children.

The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ≥0.2 µg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ≥8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ≥8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D.

Prevalence of pneumococcal bacteremia among children <36 months of age presenting with moderate fever to pediatric emergency rooms of the Metropolitan Region (Santiago), Chile.

Blood culture collection from outpatients < age 36 months with high fever (>40 degrees C, rectal) became a standard of ambulatory care in Emergency Rooms (ERs) of the government Children's Hospitals in Chile's Metropolitan Region (MR) in 1999; thereafter, invasive pneumococcal disease (IPD) incidence doubled over preceding years' estimates limited to hospitalizations. We studied IPD among children with moderate (>39 degrees C but <40 degrees C, rectal) rather than high fever visiting Pediatric ERs. Recruitment ensued Monday to Friday, 1-5 PM, September 1, 2002 through August 31, 2003. Age <36 months; rectal temperature >39 degrees but <40 degrees C; outpatient management; parental consent for hemoculture were inclusion criteria. Thirteen-thousand five hundred seventy-seven children < age 36 months with moderate and 3,214 children with high fever sought ER care. Of 1,134 moderate fever children seen in ERs during the enrollment, parents of 837 consented (73.8%). During these days and hours, 714 children < age 36 months presented with high fever and 651 (91.2%) had a "routine" blood culture. Pneumococcemia was detected among 0.7% with moderate and 1.2% with high fever (6/837 vs 8/651, p > 0.05). Extrapolating these rates to all ER outpatients < age 36 months with moderate and high fever, we estimate the true burden as 95 and 39 cases, respectively. The burden of pediatric IPD in the MR is currently underestimated because bacteremias among ER outpatients with moderate fever are not detected. If blood cultures were systematically collected from outpatients with moderate fever, recorded pediatric IPD burden would rise >2-fold. However, economic and logistical constraints preclude such a practice.