title: Pneumococcal conjugate vaccine failure in children: A systematic review of the literature.
abstract: Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes.
  
  
  
  We undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles.
  
  
  
  We identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3+1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8-2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3-8.5%).
  
  
  
  Pneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries with established pneumococcal vaccination programmes.
authors.affiliation: Paediatric Infectious Disease Research Group, St. George's University of London, United Kingdom.
authors.forename: Godwin
authors.initials: G
authors.lastname: Oligbu
authors.affiliation: Paediatric Infectious Disease Research Group, St. George's University of London, United Kingdom. Electronic address: yhsia@sgul.ac.uk.
authors.forename: Yingfen
authors.initials: Y
authors.lastname: Hsia
authors.affiliation: Paediatric Infectious Disease Research Group, St. George's University of London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Folgori
authors.affiliation: Immunisation, Hepatitis, and Blood Safety Department, Public Health of England, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Collins
authors.affiliation: Paediatric Infectious Disease Research Group, St. George's University of London, United Kingdom; Immunisation, Hepatitis, and Blood Safety Department, Public Health of England, United Kingdom.
authors.forename: Shamez
authors.initials: S
authors.lastname: Ladhani
mesh_terms: D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D017211:Treatment Failure; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: C586648:10-valent pneumococcal conjugate vaccine; C538862:13-valent pneumococcal vaccine; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Children; Conjugate pneumococcal vaccine; Pneumococcal invasive disease; Systematic review; Vaccine failure