Abstract

BackgroundPeriodic cycles in the serotype-specific incidence of invasive pneumococcal disease have been described but less is known in carriage.MethodsWe analyzed serotype carriage prevalence among children 0–6 years old over a 15-year period that included pre-PCV7 data and a decade of PCV7 use. Mixed generalized additive models were used to study periodic cycles and how PCV7 impacted on them.ResultsPneumococcal carriage data of 7,463 children were analyzed. Periodic cycles ranging from 3 to 6 years were observed for PCV7-serotypes (VT) 14, 19F and 23F and for non-PCV7 types (NVT) 3, 6A, 6C, 11A, and NT. An indirect impact of PCV7 on periodic cycles of NVT was observed and could be translated in three ways: (i) a higher amplitude in the PCV7 period (serotypes 3 and 11A), (ii) sustained increase in the prevalence of carriage (serotypes 6C, 19A and NT) and (iii) an increase in the inter-epidemic period (serotypes 3, 6A and NT). An increase in the child’s mean age of carriage of VTs 6B, 19F and 23F was observed. Serotypes 3, 6C, 11A and 15A became more frequent in ages previously associated with carriage of VTs.ConclusionsPeriodic cycles among serotypes frequently carried exist and can be modeled. These cycles can be perturbed upon introduction of PCVs and can lead to shifts in the mean age of carriage. Cyclic re-emergence of VTs can occur in settings with non-universal vaccine use. These results should be taken into account when interpreting surveillance data on pneumococcal carriage.

Highlights

  • Streptococcus pneumoniae is an obligate colonizer of humans and is commonly isolated from the nasopharynx of children younger than 6 years old [1]

  • Periodic cycles ranging from 3 to 6 years were observed for PCV7-serotypes (VT) 14, 19F and 23F and for non-PCV7 types (NVT) 3, 6A, 6C, 11A, and NT

  • Periodic cycles among serotypes frequently carried exist and can be modeled. These cycles can be perturbed upon introduction of PCVs and can lead to shifts in the mean age of carriage

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Summary

Results

Between 1996 and 2010, 7,463 nasopharyngeal samples were obtained from children attending 39 day-care centers. Comparison of the mean age of carriage of PCV7 serotypes between the high-vaccine and pre-vaccine periods indicated that it increased significantly for serotypes 6B (from 2.8 to 4.2 yrs), 19F (from 3.0 to 3.7 yrs) and 23F (from 2.9 to 3.9 yrs) (Table 3). Comparison of the mean age of carriage of PCV13 serotypes not targeted by PCV7 between the high-vaccine and pre-vaccine periods indicated that the mean age of carriage decreased significantly for serotype 3 (from 4.4 to 3.9 yrs) (Table 3, S1 Fig). The prevalence of serotypes 6C, 15B/C and NT was found to be associated with the vaccine period after adjusting for the child’s age, calendar year and day-care center (Table 2). No differences in the mean age of carriage for the other non-vaccine serotypes were found (Table 3, S1 Fig)

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