Whooping cough outbreaks in 2024. Can immunisation strategies be improved?

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Can immunisation strategies be improved?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "149" "paginaFinal" => "151" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Fernando Moraga-Llop" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Fernando" "apellidos" => "Moraga-Llop" "email" => array:1 [ 0 => "fernandomoragallop@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Societat Catalana de Pediatria, Asociación Española de Vacunología, Barcelona, Spain" "identificador" => "af0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Brotes de tosferina en 2024. ¿Se puede mejorar la estrategia de vacunación?" ] ] "textoCompleto" => "Whooping cough is a toxin-mediated, acute respiratory disease caused by Bordetella pertussis that remains a global public health problem. Other species of the genus Bordetella (B. parapertussis, B. bronchiseptica, and B. holmesii) and other microorganisms, mainly viruses (adenovirus, respiratory syncytial virus, and parainfluenza virus, among others) can cause clinical symptoms similar to pertussis, but milder and of shorter duration, called pertussis-like or pertussis-like syndrome. In some cases, co-infection occurs with B. pertussis and a virus, and sometimes with B. pertussis, and B. parapertussis.<a class="elsevierStyleCrossRef" href="#bb0005">1</a>,<a class="elsevierStyleCrossRef" href="#bb0010">2</a>Whooping cough is highly contagious, with a basic reproduction number (Ro),the average number of new cases generated by an infected patient in a susceptible population, of between 12 and 17 persons, which is the highest along with measles. The disease is transmitted by direct contact through respiratory secretions of infected persons. Transmission rates of 50%–80% have been reported in school settings.<a class="elsevierStyleCrossRef" href="#bb0010">2</a> In Spain, it has been a notifiable disease since 1982 and individually notifiable since 1997.Whooping cough is an endemic disease, with cyclical epidemic waves every 3–5 years, occurring throughout the year, but especially (to date) in spring and early summer (although the current epidemic wave in Spain started in autumn 2023).<a class="elsevierStyleCrossRef" href="#bb0015">3</a> Neither the disease nor vaccination provides long-lasting immunity; with vaccination, a loss of immunity over time has been observed, which is more evident since the acellular vaccine has been used rather than the whole-cell vaccine, and it is also less effective.<a class="elsevierStyleCrossRef" href="#bb0010">2</a>,<a class="elsevierStyleCrossRef" href="#bb0020">4</a>In the 21st century, the two clinical problems of whooping cough in developed countries are, firstly, in newborns and infants under 3 months of age, due to the severity and lethality of the disease, and secondly, in pre-adolescents and adolescents, due to the higher incidence and outbreaks in schools and families that require diagnosis, contact studies, follow-up, and the establishment of isolation and chemoprophylaxis through epidemiological surveillance and public health services to control them. These interventions have a major impact on the health system.In Spain, severe complications in infants under 3 months of age (malignant pertussis syndrome) are very rare since vaccination against pertussis was implemented in pregnant women, which began in 2014 in Catalonia and was completed nationwide in 2016, with excellent coverage (87.2% in 2022).<a class="elsevierStyleCrossRef" href="#bb0025">5</a> In 2023, only one death occurred in a newborn whose mother had not been vaccinated during pregnancy; the highest number of reported deaths was observed in 2011 and 2015, at eight per year.<a class="elsevierStyleCrossRef" href="#bb0015">3</a>Another cause for concern and burden on the health system in Spain is the annual occurrence, but with varying intensity, of school and family outbreaks that disrupt the life of families and schools. One of the causes of these outbreaks is that from 5 years after the last dose of the calendar vaccine, given at 6 years of age, there is a significant decrease in immunity and in the duration of protection.<a class="elsevierStyleCrossRef" href="#bb0010">2</a>,<a class="elsevierStyleCrossRef" href="#bb0020">4</a> In this age group, between 10 and 14 years of age, most cases occur in the form of outbreaks in schools, which accounted for 36.3% of reported cases in all age groups in 2023 (39.3% in Catalonia in the period 2023–2024) and which increased more in recent years than in other age groups.<a class="elsevierStyleCrossRef" href="#bb0015">3</a>,<a class="elsevierStyleCrossRef" href="#bb0030">6</a>This epidemiological situation, which is well known, has increased since the end of 2023 and has become overwhelmed in these first weeks of 2024 by the very high number of outbreaks and cases. In Catalonia, by 27 March, 7230 cases had been reported,<a class="elsevierStyleCrossRef" href="#bb0030">6</a> and in Spain, by 3 March, 6800 cases had been reported,<a class="elsevierStyleCrossRef" href="#bb0035">7</a>,<a class="elsevierStyleCrossRef" href="#bb0040">8</a> higher than the annual figures for the last 20 years, with the exception of 2015, when there were 3848 and 9234 cases, respectively.<a class="elsevierStyleCrossRefs" href="#bb0030">6–8</a> This situation has been reported in the media since the first major outbreak, which started in January in Guadalajara, and has already affected more than 500 people.Pertussis is also significantly under-reported<a class="elsevierStyleCrossRef" href="#bb0045">9</a> and most of the reported cases are laboratory-confirmed, which requires a polymerase chain reaction (PCR) test or nasopharyngeal swab sample. In 2023, 2560 cases were reported, of which 1958 (76.5%) were confirmed (97.2% by PCR).<a class="elsevierStyleCrossRef" href="#bb0015">3</a> However, there is a significant number of suspected cases (cough for at least two weeks duration with one of these features: paroxysmal cough, inspiratory stridor, cough-induced vomiting, or episodes of apnoea, a definition that often does not coincide with the clinical presentation of the child) not confirmed bacteriologically, and which are not reported. This under-reporting could mean that there are at least three times or more cases than reported..<a class="elsevierStyleCrossRef" href="#bb0045">9</a>It is also widely believed that whooping cough is a childhood disease, when in fact it affects all age groups. However, it is most often identified in children, as in adolescents and adults it often evolves as a prolonged non-specific cough that goes undiagnosed, and this is another reason that it is under-reported. Whooping cough is usually milder in adolescents, adults, and vaccinated people.<a class="elsevierStyleCrossRef" href="#bb0005">1</a>,<a class="elsevierStyleCrossRef" href="#bb0010">2</a>Re-emergence of pertussis has been observed since the 1990s in the United States, with a shift of cases to the adolescent and young adult age groups.<a class="elsevierStyleCrossRef" href="#bb0020">4</a>,<a class="elsevierStyleCrossRefs" href="#bb0050">10–13</a> The beginning of the 21st century saw a resurgence in Europe; in Spain, pertussis has been in a sustained epidemic situation since 2011 (3124 cases, 6.7 per 100,000 inhabitants). The cyclical pattern is maintained and at higher rates than in previous epidemic periods. Peak incidence (19.9 cases per 100,000 population) was in 2015, with 9234 cases reported.<a class="elsevierStyleCrossRef" href="#bb0040">8</a> From March 2020, coinciding with the COVID-19 pandemic, B. pertussis circulation declined dramatically (as with other respiratory diseases), but 2023 saw a significant increase in the number of cases and outbreaks, especially in the last quarter, which has continued, most notably, in the first quarter of 2024, indicating that a new epidemic wave has begun.<a class="elsevierStyleCrossRef" href="#bb0035">7</a>,<a class="elsevierStyleCrossRef" href="#bb0040">8</a>Vaccination against pertussis started in Spain in 1965 in the form of vaccination campaigns, and since 1975 has been part of successive routine vaccination schedules, with the whole-cell vaccine (DTwP or DTcP vaccine, containing inactivated B. pertussis), a vaccine approved in 1944.<a class="elsevierStyleCrossRef" href="#bb0020">4</a> The replacement by the acellular vaccine (DTaP, with two to five antigenic components of the bacterium), which is less reactogenic, but also less immunogenic and effective than the whole-cell vaccine,<a class="elsevierStyleCrossRef" href="#bb0020">4</a>,<a class="elsevierStyleCrossRef" href="#bb0070">14</a> was made in the immunisation schedule of the Spanish Association of Paediatrics in 1995 and in that of the Interterritorial Council of the Spanish National Health System in 2005, although 3 years earlier it had already been changed in some autonomous communities.<a class="elsevierStyleCrossRef" href="#bb0075">15</a> Another important change was that primary vaccination with three doses (at 2, 4, and 6 months) was changed to two doses from the 2017 schedule.<a class="elsevierStyleCrossRef" href="#bb0040">8</a>The 2024 common schedule of vaccinations and lifelong immunisations of the Interterritorial Council of the Spanish National Health System, in addition to vaccination of pregnant women, recommends four doses of pertussis vaccine in children: two doses at first vaccination, at 2 and 4 months, and two booster doses at 11 months and 6 years of age. However, since 2003, the Spanish Association of Paediatrics has recommended a booster dose for adolescents, at 12–14 years of age. Only the autonomous community of Asturias, since 2015, has included a third booster dose in its schedule at 13 years of age; Ceuta in 2002, and subsequently Melilla in 2008, and Madrid, in 2011, included a dose in adolescence that was later discontinued.<a class="elsevierStyleCrossRef" href="#bb0075">15</a>Vaccination coverage in Spain in 2022 was over 95% for the first three doses, but fell to 90.7% for 6-year-olds. It should be noted that coverage for 6-year-olds, in six autonomous communities is below 80%, and in nine it is between 80% and 90%. This coverage should be urgently improved, as should the already good coverage for pregnant women (87.2%).<a class="elsevierStyleCrossRef" href="#bb0025">5</a>The current vaccination strategy with the available vaccines has two areas for improvement. First, coverage of the booster dose at 6 years of age, the last dose to be administered in the schedule, should be increased and the normal B. pertussis-containing MMR vaccine (DTaP) should always be used. Secondly, a booster dose should be administered at the start of pre-adolescence, at 10–11 years of age, 4–5 years after the last dose. The purpose of this booster dose is to protect the individual adolescent and, above all, to minimise the occurrence of school and family outbreaks. However, knowing that B. pertussis will continue to circulate, and the disease will move to young and older adults, the revaccination of adults should also be considered.Eighty years after the introduction of the whole-cell pertussis vaccine,<a class="elsevierStyleCrossRef" href="#bb0020">4</a> which was highly successful in reducing disease-associated morbidity and mortality worldwide, B. pertussis remains a major public health problem. Current vaccines do not prevent infection as they do not act on nasopharyngeal colonisation, and a vaccinated person can become infected, be an asymptomatic carrier, and transmit the infection.<a class="elsevierStyleCrossRef" href="#bb0080">16</a> Therefore, new vaccines are needed for booster doses that are monovalent (current vaccines are part of combination vaccines: hexavalent in the first year of life and tri- or tetravalent in older children), for adolescents and adults, and that provide sterilising immunity to prevent infection. Among the vaccines under investigation,<a class="elsevierStyleCrossRef" href="#bb0020">4</a>,<a class="elsevierStyleCrossRefs" href="#bb0085">17–19</a> BPZE1<a class="elsevierStyleCrossRef" href="#bb0100">20</a> is the most advanced in development and, due to its mechanism of action, can control infection by inducing sterilising immunity.BPZE1 vaccine, which is administered intranasally and contains a live attenuated and modified strain of B. pertussis with the pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin removed or inactivated by genetic mechanisms, has shown good results in a phase IIb clinical trial. The vaccine induced a large and consistent mucosal secretory IgA response and was well tolerated. The authors of the study conclude that the attenuated intranasal vaccine produced functional immune responses that may prevent B. pertussis infections and ultimately reduce transmission and decrease epidemic cycles; these results form the basis for the initiation of phase III.<a class="elsevierStyleCrossRef" href="#bb0100">20</a>Whooping cough and mumps are the most poorly controlled immunopreventable diseases and the most resistant to vaccination.<a class="elsevierStyleCrossRef" href="#bb0080">16</a> Available pertussis vaccines cannot definitively prevent or eliminate the disease. New vaccines are needed that act not only to prevent disease but also infection, thus preventing transmission and circulation of B. pertussis. In addition, new lifelong vaccination strategies should be recommended. This message has been repeated over the last 15 years.<a class="elsevierStyleCrossRef" href="#bb0060">12</a>,<a class="elsevierStyleCrossRef" href="#bb0095">19</a>,<a class="elsevierStyleCrossRef" href="#bb0105">21</a>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cambios etiológicos, manifestaciones infrecuentes y presentaciones atípicas de enfermedades infecciosas frecuentes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Martínez Roig" 1 => "F. 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