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. 2012 Jul;23(4):510-9.
doi: 10.1097/EDE.0b013e31824f2f32.

Estimating Rates of Carriage Acquisition and Clearance and Competitive Ability for Pneumococcal Serotypes in Kenya With a Markov Transition Model

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Free PMC article

Estimating Rates of Carriage Acquisition and Clearance and Competitive Ability for Pneumococcal Serotypes in Kenya With a Markov Transition Model

Marc Lipsitch et al. Epidemiology. .
Free PMC article

Erratum in

  • Epidemiology. 2013 Jan;24(1):177

Abstract

Background: There are more than 90 serotypes of Streptococcus pneumoniae, with varying biologic and epidemiologic properties. Animal studies suggest that carriage induces an acquired immune response that reduces duration of colonization in a nonserotype-specific fashion.

Methods: We studied pneumococcal nasopharyngeal carriage longitudinally in Kenyan children 3-59 months of age, following up positive swabs at days 2, 4, 8, 16, and 32 and then monthly thereafter until 2 swabs were negative for the original serotype. As previously reported, 1868/2840 (66%) of children swabbed at baseline were positive. We estimated acquisition, clearance, and competition parameters for 27 serotypes using a Markov transition model.

Results: Point estimates of type-specific acquisition rates ranged from 0.00025/d (type 1) to 0.0031/d (type 19F). Point estimates of time to clearance (inverse of type-specific immune clearance rate) ranged from 28 days (type 20) to 124 days (type 6A). For the serotype most resistant to competition (type 19F), acquisition of other serotypes was 52% less likely (95% confidence interval = 37%-63%) than in an uncolonized host. Fitness components (carriage duration, acquisition rate, lack of susceptibility to competition) were positively correlated with each other and with baseline prevalence, and were associated with biologic properties previously shown to associate with serotype. Duration of carriage declined with age for most serotypes.

Conclusions: Common S. pneumoniae serotypes appear superior in many dimensions of fitness. Differences in rate of immune clearance are attenuated as children age and become capable of more rapid clearance of the longest-lived serotypes. These findings provide information for comparison after introduction of pneumococcal conjugate vaccine.

Figures

Figure 1
Figure 1
Structure of the Markov transition model for the situation in which two serotypes plus “other” are considered. The model used in the text was similar except that 27 serotypes plus “other” were considered.
Figure 2
Figure 2
Parameter estimates (with 95% confidence intervals) by serotype, with serotypes ordered from most to least prevalent. A. Mean time to immune clearance bi . B. Acquisition rate ai . C. Susceptibility to competition ri
Figure 3
Figure 3
Parameter estimates (with 95% confidence intervals) by serotype and age tercile, with the top 14 serotypes ordered from most to least prevalent. A. Mean time to immune clearance bi . B. Acquisition rate ai . C. Susceptibility to competition ri *Susceptibility of 15A at <22 months (not shown) estimated at 0.004741
Figure 4
Figure 4
Number of hosts in whom each serotype was isolated at baseline, compared with the ratio of hosts in whom it was isolated at baseline vs. followup (note log scale on y axis). For rarer serotypes, there was no tendency to be more common at baseline or at followup, whereas more common serotypes tended to be isolated more often at baseline than followup.

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