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      Field Evaluation of Culture plus Latex Sweep Serotyping for Detection of Multiple Pneumococcal Serotype Colonisation in Infants and Young Children

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          Abstract

          Background

          Nasopharyngeal swab (NPS) culture by World Health Organisation (WHO) methodology underestimates multiple pneumococcal serotype colonisation compared to a simple culture and latex sweep method. The impacts of this on descriptions of pneumococcal serotype distributions and colonisation dynamics in infancy are not clear.

          Methods

          8,736 NPS collected from infants enrolled into a longitudinal study were processed to evaluate the field utility of the latex sweep method. 1,107 had previously been cultured by WHO methodology. Additionally, colonisation results were compared in 100 matched pairs of infants, where swabs from an individual were cultured either by WHO or latex sweep method.

          Results

          In 1,107 swabs cultured by both methods, the latex sweep method was three times more likely to detect colonisation with multiple pneumococcal serotypes than the WHO method (p<0.001). At least one common serotype was identified in 91.2% of swabs from which typeable pneumococci were detected by both methods. Agreement improved with increasing colonisation density (p = 0.03). Estimates of age at first pneumococcal acquisition and colonisation duration were not affected by culture/serotyping method. However, a greater number of serotype carriage episodes were detected in infants cultured by latex sweep (p = 0.03). The overall rate of non-vaccine type pneumococcal acquisition was also greater in infants cultured by latex sweep (p = 0.04).

          Conclusions

          Latex sweep serotyping was feasible to perform on a large specimen collection. Multiple serotype colonisation detection was significantly improved compared with WHO methodology. However, use of the latex sweep method is unlikely to significantly alter colonisation study serotype distribution or colonisation dynamics results.

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          Most cited references26

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          Streptococcus pneumoniae colonisation: the key to pneumococcal disease.

          Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. The burden of disease is highest in the youngest and oldest sections of the population in both more and less developed countries. The treatment of pneumococcal infections is complicated by the worldwide emergence in pneumococci of resistance to penicillin and other antibiotics. Pneumococcal disease is preceded by asymptomatic colonisation, which is especially high in children. The current seven-valent conjugate vaccine is highly effective against invasive disease caused by the vaccine-type strains. However, vaccine coverage is limited, and replacement by non-vaccine serotypes resulting in disease is a serious threat for the near future. Therefore, the search for new vaccine candidates that elicit protection against a broader range of pneumococcal strains is important. Several surface-associated protein vaccines are currently under investigation. Another important issue is whether the aim should be to prevent pneumococcal disease by eradication of nasopharyngeal colonisation, or to prevent bacterial invasion leaving colonisation relatively unaffected and hence preventing the occurrence of replacement colonisation and disease. To illustrate the importance of pneumococcal colonisation in relation to pneumococcal disease and prevention of disease, we discuss the mechanism and epidemiology of colonisation, the complexity of relations within and between species, and the consequences of the different preventive strategies for pneumococcal colonisation.
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            Serotype replacement in disease after pneumococcal vaccination.

            Vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of pneumococcal disease and has had an important public health benefit. Because this vaccine targets only seven of the more than 92 pneumococcal serotypes, concerns have been raised that non-vaccine serotypes (NVTs) could increase in prevalence and reduce the benefits of vaccination. Indeed, among asymptomatic carriers, the prevalence of NVTs has increased substantially, and consequently, there has been little or no net change in the bacterial carriage prevalence. In many populations, pneumococcal disease caused by NVT has increased, but in most cases this increase has been less than the increase in NVT carriage. We review the evidence for serotype replacement in carriage and disease, and address the surveillance biases that might affect these findings. We then discuss possible reasons for the discrepancy between near-complete replacement in carriage and partial replacement for disease, including differences in invasiveness between vaccine serotypes. We contend that the magnitude of serotype replacement in disease can be attributed, in part, to a combination of lower invasiveness of the replacing serotypes, biases in the pre-vaccine carriage data (unmasking), and biases in the disease surveillance systems that could underestimate the true amount of replacement. We conclude by discussing the future potential for serotype replacement in disease and the need for continuing surveillance. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Report from a WHO Working Group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae.

              Numerous studies evaluating the efficacy of conjugate pneumococcal vaccines are being conducted or planned throughout the world. Some of these studies are evaluating the effect of vaccine on nasopharyngeal (NP) carriage. The World Health Organization established a Working Group comprised of representatives from these trials and other NP colonization experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in these trials. The intent was to reduce or eliminate variability in key methods which themselves could contribute to variability of observed pneumococcal NP colonization. In this way variability of vaccine effects between trials on NP colonization could more easily be analyzed for population or vaccine differences without the confounding effect caused by differences in study methodology. This paper presents the evidence base supporting the need for standardized NP colonization study methods, the methods themselves (Core Consensus Methods), including collection techniques, culture media, equipment, serotyping, storage of specimens and transport of isolates agreed on by the Working Group as well as a discussion of research priorities. The Core Consensus Methods provide a common methodology to conduct pneumococcal NP colonization studies with minimum interstudy method variability. The intention is to allow more meaningful comparisons of study results from conjugate pneumococcal vaccine trials.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                2 July 2013
                : 8
                : 7
                : e67933
                Affiliations
                [1 ]Shoklo Malaria Research Unit, Mae Sot, Thailand
                [2 ]Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
                [3 ]Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom
                [4 ]Immunobiology Unit, Institute of Child Health, University College London, London, United Kingdom
                Centers for Disease Control & Prevention, United States of America
                Author notes

                Competing Interests: Francois Nosten has served as an editor for PLOS ONE. This does not alter the authors‚ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: PT CT FN DG. Performed the experiments: PT CT AJ KP. Analyzed the data: PT. Wrote the paper: PT.

                [¤]

                Current address: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia

                Article
                PONE-D-13-15590
                10.1371/journal.pone.0067933
                3699458
                23844133
                55c666f8-994b-4cb0-bf99-1deb71566c84
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 April 2013
                : 23 May 2013
                Page count
                Pages: 7
                Funding
                This work was supported by the Wellcome Trust of Great Britain (Grant No. 083735/Z/07/Z to PT) and the Li Ka Shing Foundation – University of Oxford Global Health Programme (Grant No. LKS-SM09 to AJ and PT). SMRU is part of the Mahidol Oxford University Research Unit and is supported by the Wellcome Trust of Great Britain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Microbiology
                Bacterial Pathogens
                Streptococci
                Population Biology
                Population Dynamics
                Disease Dynamics
                Medicine
                Clinical Immunology
                Immunity
                Immunizations
                Infectious Diseases
                Bacterial Diseases
                Pneumococcus
                Pediatrics
                Public Health
                Child Health
                Immunizations

                Uncategorized
                Uncategorized

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