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      PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear

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          Abstract

          Otitis media (OM) is a major reason for antibiotic consumption and surgery in children. Nasopharyngeal carriage of otopathogens, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi), is a prerequisite for development of OM, and increased nasopharyngeal otopathogen density correlates with disease onset. Vaccines can reduce or eliminate otopathogen carriage, as demonstrated for pneumococcal serotypes included in pneumococcal conjugate vaccines (PCV). The 10-valent PCV (PCV10) includes an NTHi carrier protein, and in 2011 superseded 7-valent PCV on the New Zealand Immunisation Program. Data are conflicting on whether PCV10 provides protection against NTHi carriage or disease. Assessing this in otitis-prone cohorts is important for OM prevention. We compared otopathogen density in the nasopharynx and middle ear of New Zealand PCV7-vaccinated and PCV10-vaccinated otitis-prone and non-otitis-prone children to determine PCV10 impact on NTHi and S. pneumoniae carriage. We applied qPCR to specimens collected from 217 PCV7-vaccinated children (147 otitis-prone and 70 non-otitis-prone) and 240 PCV10-vaccinated children (178 otitis-prone and 62 non-otitis-prone). After correcting for age and day-care attendance, no difference was observed between NTHi density in the nasopharynx of PCV7-vaccinated versus PCV10-vaccinated otitis-prone ( p = 0.563) or non-otitis-prone ( p = 0.513) children. In contrast, pneumococcal nasopharyngeal density was higher in PCV10-vaccinated otitis-prone children than PCV7-vaccinated otitis-prone children ( p = 0.003). There was no difference in otopathogen density in middle ear effusion from PCV7-vaccinated versus PCV10-vaccinated otitis-prone children (NTHi p = 0.918; S. pneumoniae p = 0.415). When pneumococcal carriage was assessed by vaccine serotypes (VT) and non-vaccine serotypes (NVT), there was no difference in VT density ( p = 0.546) or NVT density ( p = 0.315) between all PCV7-vaccinated versus all PCV10-vaccinated children. In summary, PCV10 did not reduce NTHi density in the nasopharynx or middle ear, and was associated with increased pneumococcal nasopharyngeal density in otitis-prone children in New Zealand. Development of therapies that prevent or reduce otopathogen colonisation density in the nasopharynx are warranted to reduce the burden of OM.

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          Efficacy of a pneumococcal conjugate vaccine against acute otitis media.

          Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.
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            Otitis media.

            Otitis media (OM) continues to be one of the most common childhood infections and is a major cause of morbidity in children. The pathogenesis of OM is multifactorial, involving the adaptive and native immune system, Eustachian-tube dysfunction, viral and bacterial load, and genetic and environmental factors. Initial observation seems to be suitable for many children with OM, but only if appropriate follow-up can be assured. In children younger than 2 years with a certain diagnosis of acute OM, antibiotics are advised. Surgical candidacy depends on associated symptoms, the child's developmental risk, and the anticipated chance of timely spontaneous resolution of the effusion. The recommended approach for surgery is to start with tympanostomy tube placement, eventually followed by adenoidectomy. The ideal intervention for OM, however, does not yet exist, and an urgent need remains to explore new and creative options based on modern insights into the pathophysiology of OM.
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              Trends in antimicrobial prescribing rates for children and adolescents.

              Annual rates of antimicrobial prescribing for children by office-based physicians increased from 1980 through 1992. The development of antimicrobial resistance, which increased for many organisms during the 1990s, is associated with antimicrobial use. To combat development of antimicrobial resistance, professional and public health organizations undertook efforts to promote appropriate antimicrobial prescribing. To assess changes in antimicrobial prescribing rates overall and for respiratory tract infections for children and adolescents younger than 15 years. National Ambulatory Medical Care Survey data provided by 2500 to 3500 office-based physicians for 6500 to 13 600 pediatric visits during 2-year periods from 1989-1990 through 1999-2000. Population- and visit-based antimicrobial prescribing rates overall and for respiratory tract infections (otitis media, pharyngitis, bronchitis, sinusitis, and upper respiratory tract infection) among children and adolescents younger than 15 years. The average population-based annual rate of overall antimicrobial prescriptions per 1000 children and adolescents younger than 15 years decreased from 838 (95% confidence interval [CI], 711-966) in 1989-1990 to 503 (95% CI, 419-588) in 1999-2000 (P for slope <.001). The visit-based rate decreased from 330 antimicrobial prescriptions per 1000 office visits (95% CI, 305-355) to 234 (95% CI, 210-257; P for slope <.001). For the 5 respiratory tract infections, the population-based prescribing rate decreased from 674 (95% CI, 568-781) to 379 (95% CI, 311-447; P for slope <.001) and the visit-based prescribing rate decreased from 715 (95% CI, 682-748) to 613 (95% CI, 570-657; P for slope <.001). Both population- and visit-based prescribing rates decreased for pharyngitis and upper respiratory tract infection; however, for otitis media and bronchitis, declines were only observed in the population-based rate. Prescribing rates for sinusitis remained stable. The rate of antimicrobial prescribing overall and for respiratory tract infections by office-based physicians for children and adolescents younger than 15 years decreased significantly between 1989-1990 and 1999-2000.
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                Author and article information

                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                31 January 2019
                March 2019
                : 7
                : 1
                : 14
                Affiliations
                [1 ]School of Medicine, University of Western Australia, Perth 6009, Australia; camilla.degier@ 123456uwa.edu.au (C.d.G.); mejbah.bhuiyan@ 123456uwa.edu.au (M.B.); peter.richmond@ 123456uwa.edu.au (P.C.R.); ruth.thornton@ 123456uwa.edu.au (R.B.T.)
                [2 ]Wesfarmers Centre of Vaccines and Infectious Disease, Telethon Kids Institute, Perth 6009, Australia; caitlyn.granland@ 123456telethonkids.org.au (C.M.G.); janessa.pickering@ 123456telethonkids.org.au (J.L.P.)
                [3 ]Department of Paediatrics, University of Otago, Christchurch 8011, New Zealand; tony.walls@ 123456otago.ac.nz
                [4 ]Starship Hospital, Auckland 1023, New Zealand; Nikki@ 123456adhb.govt.nz (N.M.); e.best@ 123456auckland.ac.nz (E.J.B.)
                [5 ]School of Medicine, University of Auckland, Auckland 1023, New Zealand
                [6 ]Department of General Paediatrics, Perth Children’s Hospital, Perth 6009, Australia
                [7 ]Centre for Child Health Research, University of Western Australia, Perth 6009, Australia
                Author notes
                Author information
                https://orcid.org/0000-0001-5421-8126
                Article
                vaccines-07-00014
                10.3390/vaccines7010014
                6466140
                30708945
                0f4f1f5c-a9fb-418d-b57c-d225e2c81321
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 November 2018
                : 29 January 2019
                Categories
                Article

                carriage density,nasopharynx,new zealand,otitis media,pneumococcal conjugate vaccine,nthi,qpcr

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