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

Lipsitch, Marca,b; Abdullahi, Osmanb,c; D'Amour, Alexanderd; Xie, Wenb; Weinberger, Daniel M.b,e; Tchetgen Tchetgen, Erica,f; Scott, J. Anthony G.c,g

Erratum

The RData files were omitted from the supplementary material that was posted online with this paper. These files can be found here: http://links.lww.com/EDE/A632.

Epidemiology. 24(1):177, January 2013.

doi: 10.1097/EDE.0b013e31824f2f32
Infectious Disease

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.

From the aCenter for Communicable Disease Dynamics and Department of Epidemiology, Harvard School of Public Health, Boston, MA; bDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA; cKenya Medical Research Institute–Wellcome Trust Research Programme, Kilifi, Kenya; dDepartment of Statistics, Harvard University, Cambridge, MA; eDivision of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD; fDepartment of Biostatistics, Harvard School of Public Health, Boston, MA; and gNuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.

Submitted 28 October 2011; accepted 26 January 2012; posted 21 March 2012.

Supported by research grant R01 AI04893 from the US National Institutes of Health (to M.L.) and by a clinical fellowship from the Wellcome Trust of Great Britain (No. 081835) (to J.A.G.S.). M.L. has received consulting fees or honoraria from Pfizer, Novartis, Outcome Sciences, and AIR Worldwide. J.A.G.S. has received grant funding from GlaxoSmithKline and has received study vaccines without cost from Pfizer/Wyeth. The authors reported no other financial interests related to this research.

This paper is published with the permission of the Director of the Kenya Medical Research Institute.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Editor's note: A commentary on this article appears on page 520.

Correspondence: Marc Lipsitch, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115. E-mail: mlipsitc@hsph.harvard.edu.

© 2012 Lippincott Williams & Wilkins, Inc.