Rates of acquisition and clearance of pneumococcal serotypes in the nasopharynges of children in Kilifi District, Kenya

Abstract

Background: To understand and model the impact of pneumococcal conjugate vaccines at the population level, we need to know the transmission dynamics of individual pneumococcal serotypes. We estimated serotype-specific clearance and acquisition rates of nasopharyngeal colonization among Kenyan children.

Methods: Children aged 3-59 months who were identified as carriers in a cross-sectional survey were followed-up approximately 1, 2, 4, 8, 16, and 32 days later and monthly thereafter until culture of 2 consecutive swabs yielded an alternative serotype or no pneumococcus. Serotype-specific clearance rates were estimated by exponential regression of interval-censored carriage durations. Duration was estimated as the reciprocal of the clearance rate, and acquisition rates were estimated on the basis of prevalence and duration, assuming an equilibrium state.

Results: Of 2840 children sampled between October 2006 and December 2008, 1868 were carriers. The clearance rate was 0.032 episodes/day (95% confidence interval [CI], .030-.034), for a carriage duration of 31.3 days, and the rate varied by serotype (P< .0005). Carriage durations for the 28 serotypes with ≥ 10 carriers ranged from 6.7 to 50 days. Clearance rates increased with year of age, adjusted for serotype (hazard ratio, 1.21; 95% CI, 1.15-1.27). The acquisition rate was 0.061 episodes/day (95% CI, .055-.067), which did not vary with age. Serotype-specific acquisition rates varied from 0.0002 to 0.0022 episodes/day. Serotype-specific acquisition rates correlated with prevalence (r=0.91; P< .00005) and with acquisition rates measured in a separate study involving 1404 newborns in Kilifi (r=0.87; P< .00005).

Conclusions: The large sample size and short swabbing intervals provide a precise description of the prevalence, duration, and acquisition of carriage of 28 pneumococcal serotypes. In Kilifi, young children experience approximately 8 episodes of carriage per year. The declining prevalence with age is attributable to increasing clearance rates.

Figure 1.

Flow of participants through the study.

Figure 2.

Rates of clearance and acquisition of pneumococcal colonization, by age. Abbreviation: CI, confidence interval.

Figure 3.

Rates of clearance of pneumococcal colonization by age, for immune and total clearance. Whiskers denote 95% confidence intervals.

Figure 4.

Rates of clearance and acquisition of pneumococcal colonization by serotype. Point estimates for serotypes contained in the 10-valent pneumococcal conjugate vaccine (PCV-10) are shown with open circles; those contained in the 13-valent vaccine (PCV-13) but not in the 10-valent vaccine are shown with half circles. Abbreviation: CI, confidence interval.

Figure 5.

Scatterplot and line of equality for acquisition rates estimated in 2 different studies in Kilifi. The illustration shows the scatter of acquisition rates of the most frequently observed 28 serotypes directly measured in newborns (age, 0–3 months) against the acquisition rates among children aged 3–59 months calculated in the present study. r = 0.78; P < .00005.