Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines

RESEARCH ARTICLE Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines Adamos Hadjipanayis1,2*, Elisavet Efstathiou1, Maria Alexandrou3, Loukia Panayiotou3, Chrystalla Zachariadou3, Panayiotis Petrou3, Vasiliki Papaevangelou4 a11111 1 Paediatric Department, Larnaca General Hospital, Larnaca, Cyprus, 2 European University Medical School, 6, Diogenis Street, Engomi, 1516 Nicosia, Cyprus, 3 Microbiology Laboratory, Larnaca General Hospital, Larnaca, Cyprus, 4 Third Department of Paediatrics, National and Kapodistrian University of Athens, General University Hospital “ATTIKON”, Athens, Greece * OPEN ACCESS Citation: Hadjipanayis A, Efstathiou E, Alexandrou M, Panayiotou L, Zachariadou C, Petrou P, et al. (2016) Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines. PLoS ONE 11(10): e0163269. doi:10.1371/journal.pone.0163269 Editor: Jose Melo-Cristino, Universidade de Lisboa Faculdade de Medicina, PORTUGAL Received: April 26, 2016 Accepted: September 5, 2016 Published: October 5, 2016 Copyright: © 2016 Hadjipanayis et al. 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. Data Availability Statement: The Cyprus Ethics Committee and Commissioner of Data Protection impose restrictions on these data because they include sensitive or identifying patient information. However, data are available on request from the Corresponding Author, Adamos Hadjipanayis (). Funding: Part of serotype antisera was granted by GSK, Cyprus. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Abstract The objective of the study was to describe the incidence of pneumococcal nasopharyngeal carriage, serotype distribution and antibiotic resistance profile of pneumococcal nasopharyngeal isolates in healthy children aged 6 to 36 months following the implementation of conjugate vaccines. A nasopharyngeal swab was collected from 1105 healthy children following a stratified random sampling between September 2013 and April 2014. Demographics, vaccination status and data on possible risk factors were recorded. Isolates were serotyped and tested for antibiotic susceptibility. The nasopharyngeal carriage rate was 25.3%. Among 1105 children enrolled, 393 had received PCV13 and 685 PCV10. The prevailing isolated serotypes were: 23A (14.3%), 15A (8.9%), 6C (8.6%), 23B (7.5%), 19A (5.4%) and 15B (5%). The proportion of non-vaccine serotypes, PCV10 serotypes, PCV13 additional serotypes (3, 6A, 19A) was 76.8%, 2.1% and 10.4% respectively. Although children, who were fully or partially vaccinated with PCV13, were 63% less likely to be colonized with additional PCV13 serotypes compared to those vaccinated with PCV10, the difference is not significant (95%Cl = 0.14–1.02, p = 0.053). The highest antibiotic non-susceptible rates were found for erythromycin (28.2%) and penicillin (27.9%). The overall multidrug resistance rate was 13.2%, with serotypes 24F (4/6), 15A (14/25) and 19A (6/15) being the main contributors. Carriage rate was similar between children vaccinated with PCV10 or PCV13. The high incidence of 15A serotype which is also multidrug resistant should be underlined. Ongoing surveillance is needed to monitor the dynamics on nasopharyngeal carriage. Introduction Streptococcus pneumoniae (Sp) is a common cause of childhood bacteraemia, meningitis, otitis media, pneumonia and sinusitis [1]. Young children and elderly people are at highest risk. It is PLOS ONE | DOI:10.1371/journal.pone.0163269 October 5, 2016 1 / 15 Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus, Post PCV Vaccines Competing Interests: Part of serotype antisera was granted by GSK, Cyprus. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Abbreviations: Sp, streptococcus pneumoniae; IPD, invasive pneumococcal disease; NP, nasopharyngeal; PCV7, 7-valent pneumococcal conjugate vaccine; NVT, non vaccine serotypes; PCV10, 10-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PCVs, pneumococcal conjugate vaccines; VT, vaccine serotypes. estimated that 14.5 million cases of invasive pneumococcal disease (IPD) occur annually in children aged <5 years, resulting in approximately 500,000 deaths worldwide, mainly in developing countries [1]. The human nasopharynx is the main reservoir of pneumococcal carriage. Although nasopharyngeal (NP) carriage is asymptomatic, it represents a first and necessary step for the pathogenic process of pneumococci towards IPD [2]. There is a strong association between serotype distribution of pneumococci causing invasive diseases and those colonizing the nasopharynx of children [3, 4]. Moreover, it has been documented that the antibiotic resistance profile of pneumococci colonizing the nasopharynx reflects that of the bacteria grown in children with acute otitis media [5]. The highest incidence of pneumococcal colonization occurs in young toddlers. Consequently, this risk group is the most important source of horizontal spread of pneumococcal strains within the community [2]. In order to reduce the burden of pneumococcal disease, universal infant vaccination with a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2000 in the United States, resulting in a dramatic decline of IPD not only among vaccinated children but also in unvaccinated persons of all ages through herd immunity [6–9]. However, over the next years, cases due to non-PCV7 serotype strains (especially serotype 19A), increased [10, 11]. Of note, the overall decline in IPD cases, post PCV7 implementation, was higher compared to the small increase in IPD cases due to non vaccine serotypes (NVT) [8]. Subsequently, a 10-valent pneumococcal conjugate vaccine (PCV10) and a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the routine infant immunization schedule offering wider coverage [12]. PCV10 contains three additional serotypes (1, 5, 7F) while PCV13 contains three additional serotypes to PCV10 (3, 6A, 19A). Implementation of PCV universal vaccination has led to a significant decrease of IPD incidence and reduced NP carriage of vaccine serotypes (VT) among vaccinated children [13, 14]. However, there has been a slight or no change on the prevalence of pneumococcal carriage among asymptomatic carriers [15] since NVT incidence increased while the proportion of VT was substantially reduced [16–18]. In Cyprus, PCV7 was introduced in the national vaccine schedule in February 2004. It was recommended for universal vaccination of children aged 2–23 months and for children aged 24–59 months who are at increa (...truncated)