Editorial article
Neumococcal vaccine: “the road to progress is neither fast nor easy”
Vacuna neumocócica: «El camino del progreso no es ni rápido ni fácil»
Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Son Llàtzer, Palma de Mallorca, Spain
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Only a number of them are responsible for invasive neumococcal disease (IPD) in adults and they are mostly present in the 23-valent polysaccharide vaccine (PPSV23).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> However, the use of polysaccharides as vaccine antigens has some limitations due to their low immunogenicity, inducing immune tolerance after successive administrations because, being B-cell dependent antigens, they do not generate immunological memory or mucosal immunity.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> PPSV23 was included in the adult vaccination schedule in Spain since 2003 with different implementation by each autonomous community.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> In 2009, Tarragona launched a population-based study called <span class="elsevierStyleItalic">Community-Acquired Pneumonia</span>, <span class="elsevierStyleItalic">Acute Myocardial Infarction and Stroke</span> (CAPAMIS), which it included a cohort of more than 27,000 individuals, whose main objective was to evaluate the clinical efficacy of PPSV23 in preventing a first episode of community-acquired pneumonia, acute myocardial infarction or stroke in the general population over 60 years. The results of this work were published in 2013, not observing any benefit of PPSV23 in reducing any of the 3 main objectives,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> although a protective effect against neumococcal pneumonia or from any other aetiology was observed in connection with PPSV23 in a further analysis with 3 years of follow-up.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In this issue of <span class="elsevierStyleSmallCaps">Medicina Clínica</span> the same authors are publishing a report describing the incidence, lethality and distribution of serotypes of the same cohort, CAPAMIS.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> The results show high incidence rates of neumococcal pneumonia, especially in men over 80 years of age and institutionalized. A remarkable fact is the increased rate of bacteremic pneumonia, even higher than that of a previous study in Catalonia during the period 1997–1999.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> The data provided by Vila-Corcoles et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> concerning the inefficacy of PPSV23 on the risk of non-bacteremic pneumonia would be consistent with the published literature, but differ as to the possible protective role against IPD, which, in a systematic review, showed that the PPSV23 could have greater utility.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> Therefore, the study of Vila-Corcoles et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> further confirms the need for a radical change in strategy. To try to alleviate the problems related to PPSV23, conjugate vaccines were synthesized and marketed a few years ago, consisting of the union of the capsular polysaccharide of the neumococcus to a carrier protein, generally CRM197 (diphtheria protein) in order to produce T cell stimulation, thereby inducing immunologic memory and mucosal immunity.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> Initially conjugate vaccines contained 7 serotypes and were later extended to 9, 10 and 13 serotypes. After paediatric authorization of the 7-valent conjugate vaccine (PCV7), a decrease in the rate of neumococcal disease and antibiotic resistance was observed not only in the paediatric population but also in unvaccinated adults, a phenomenon known as herd immunity, being the nasopharynx of children the main <span class="elsevierStyleItalic">S. pneumoniae</span><a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> reservoir. However, a parallel increase in infections by serotypes not included in PCV7, especially 1, 3, 7F and 19A was observed; plus, some reports showed an increased severity of neumococcal infections.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11,12</span></a> In Spain, during the period 2005–2007, increased rates of IPD in adults were observed, coinciding with the expansion of non-vaccine serotypes, and a decrease in infections caused by serotypes contained in PCV7, especially in those over 65 years of age.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> Conjugate vaccines containing these emerging serotypes started to appear in the following years and in 2010 the <span class="elsevierStyleItalic">Food and Drug Administration</span> (FDA) authorized the marketing of 13-valent conjugate vaccine (PCV13). PCV13, which also contains polysaccharides included in the PCV7 serotypes 1, 3, 5, 6A, 7F and 19A, is available in Spain since June 2010, initially for administration in paediatric population. Since then, a decline of 55% has been observed in the number of hospitalizations for IPD in children under 15 years of age and a reduction of infections, mainly those caused by serotypes 1 and 19A.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> PCV13 has also been recommended for adult patients who are immunosuppressed or with comorbidities.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">3,15</span></a> In 2014, the <span class="elsevierStyleItalic">Advisory Committee on Immunization Practices</span> (ACIP) updated recommendations for the use of PCV13 and PPSV23<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> based on the results of a double blind, randomized, placebo-controlled study entitled <span class="elsevierStyleItalic">The Community-Acquired Pneumonia Immunization Trial in Adults</span> (CAPITA), which included a total of 84,496 adults over 65 years of age, which showed that PCV13 was effective in preventing community-acquired neumococcal pneumonia (bacteremic and non-bacteremic) and serotype specific IPD.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Although the results are important, this study has some limitations as their own authors acknowledge: it was carried out in just one single country with a homogeneous population and excluded patients who developed any immune suppression after selection. In addition, the authors observed a decrease in the percentage of IPD, up to 42.3%, by serotypes contained in the PCV13 in 2013. This study, however, demonstrated no effect on community-acquired pneumonia or on any aetiology pneumonia or non-bacteremic neumococcal pneumonia and non-invasive by any serotype, nor any decrease in overall mortality caused by neumococcal pneumonia or IPD. According to data reported by Vila-Corcoles et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> the population over 80 years of age showed an increased risk of mortality. In a <span class="elsevierStyleItalic">post hoc</span> analysis of the CAPITA study, PCV13 efficacy decreased with increasing age, from 65% in 65-year-old patients to 40% in 75-year-olds.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> Another aspect is that although some published work shows that adult vaccination with PCV13 would be cost-effective,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> this analysis may vary depending on the prevalence of vaccine serotypes at any given time and place. According to Vila-Corcoles et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> 53.6% of infections were caused by serotypes included in the PCV13, although the study only covers until 2011. Based on our own experience during the period 2010–2014, we observed a trend towards a reduction of neumococcal infections caused by serotypes included in the PCV13, although these accounted for nearly 50% of the total.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It will be interesting to see the evolution of neumococcal infections in the next few years and their correlation with the degree of adherence to national and international recommendations. Vaccination of adults in our environment will depend, undoubtedly, on the vaccine's public funding capacity in the different autonomous communities. Clearly, with conjugate vaccines, we have come a long way in preventing neumococcal infections in recent years, but obtaining vaccines based on <span class="elsevierStyleItalic">S. pneumoniae</span> proteins that are more immunogenic, not serotype specific and demonstrate greater clinical efficacy should be a next step in the fight against this bacteria, but as Marie Curie said “the way of progress is neither swift nor easy”.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Payeras A, Arrizabalaga M. Vacuna neumocócica: «El camino del progreso no es ni rápido ni fácil». Med Clin (Barc). 2016;146:203–204.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "23-valent pneumococcal polysaccharide vaccine. WHO position paper" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "World Health Organization (WHO)" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Wkly Epidemiol Rec" "fecha" => "2008" "volumen" => "83" "paginaInicial" => "373" "paginaFinal" => "384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18927997" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Yother J. 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