Vaccine-induced replacement by nonvaccine serotypes in pneumococcal colonization and disease poses a threat to the long-term effectiveness of pneumococcal vaccination. One of the main drivers for serotype replacement is likely to be the competitive interactions between pneumococcal serotypes.
We used longitudinal datasets of pneumococcal colonization among infants (American Indian and The Gambia) and toddlers (Denmark) to study the strength and mechanism of competition between pneumococcal serotypes. We characterized the strength of competition as the relative reduction in the expected time spent colonized with two serotypes (double colonization) as compared with colonization with no competition. We also assessed the mechanism of competition, that is, whether reduction in double colonization is due to reduced rate of acquisition or enhanced clearance of colonization. The three datasets were analyzed assuming both perfect (100%) and imperfect (50%) sensitivity in detection of double colonization.
Each dataset showed strong between-serotype competition, and competition in acquisition was clearly identified. These findings remained in the secondary analysis assuming only 50% sensitivity to detect double colonization. Inferences about enhanced clearance due to competition were susceptible to the assumed sensitivity of detection.
Strong competition between pneumococcal serotypes can explain the prompt replacement by the nonvaccine serotypes in vaccinated persons and populations. The main mechanism of between-serotype interaction was identified as competition in acquisition, which suggests that replacement in pneumococcal disease depends largely on propensities of the replacing serotypes to cause disease through acquisition of colonization.
From the aDepartment of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland; bMedical Research Council Unit, The Gambia; cDepartment of Bacteriology, Mycology, and Parasitology, Statens Serum Institut, Copenhagen, Denmark; and dCenter for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
K.L.O. has current research funding from Pfizer and GSK and has participated on expert advisory committees for GSK, Pfizer, Aventis-Pasteur, and Merck. All other authors report no conflicts of interest.
This study was part of the research of the PneumoCarr Consortium, funded by a grant (37875) from the Bill and Melinda Gates Foundation through the Grand Challenges in Global Health Initiative. This study was also supported by the Finnish Academy (grant 138068).
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Correspondence: Juha Mehtälä, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail: firstname.lastname@example.org.
Received March 23, 2012
Accepted January 8, 2013