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1.
mBio ; 14(2): e0049923, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37036356

RESUMEN

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.


Asunto(s)
Infecciones Meningocócicas , Vacunas Meningococicas , Neisseria meningitidis Serogrupo B , Neisseria meningitidis , Lactante , Niño , Humanos , Persona de Mediana Edad , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Neisseria meningitidis/genética , Neisseria meningitidis Serogrupo B/genética , Escocia , Genómica
2.
Vaccine ; 39(11): 1621-1630, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33597116

RESUMEN

Invasive meningococcal disease (IMD) is associated with high case fatality rates and long-term sequelae among survivors. Meningococci belonging to six serogroups (A, B, C, W, X, and Y) cause nearly all IMD worldwide, with serogroup B meningococci (MenB) the predominant cause in many European countries, including Greece (~80% of all IMD). In the absence of protein-conjugate polysaccharide MenB vaccines, two protein-based vaccines are available to prevent MenB IMD in Greece: 4CMenB (Bexsero™, GlaxoSmithKline), available since 2014; and MenB-FHbp, (Trumenba™, Pfizer), since 2018. This study investigated the potential coverage of MenB vaccines in Greece using 107 MenB specimens, collected from 2010 to 2017 (66 IMD isolates and 41 clinical samples identified solely by non-culture PCR), alongside 6 MenB isolates from a carriage study conducted during 2017-2018. All isolates were characterized by multilocus sequence typing (MLST), PorA, and FetA antigen typing. Whole Genome Sequencing (WGS) was performed on 66 isolates to define the sequences of vaccine components factor H-binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria adhesin A (NadA). The expression of fHbp was investigated with flow cytometric meningococcal antigen surface expression (MEASURE) assay. The fHbp gene was present in-frame in all isolates tested by WGS and in 41 MenB clinical samples. All three variant families of fHbp peptides were present, with subfamily B peptides (variant 1) occurring in 69.2% and subfamily A in 30.8% of the samples respectively. Sixty three of 66 (95.5%) MenB isolates expressed sufficient fHbp to be susceptible to bactericidal killing by MenB-fHbp induced antibodies, highlighting its potential to protect against most IMD in Greece.


Asunto(s)
Infecciones Meningocócicas , Vacunas Meningococicas , Neisseria meningitidis Serogrupo B , Antígenos Bacterianos/genética , Europa (Continente) , Grecia/epidemiología , Humanos , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Tipificación de Secuencias Multilocus , Neisseria meningitidis Serogrupo B/genética , Estudios Retrospectivos , Serogrupo
3.
J Clin Microbiol ; 56(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29237789

RESUMEN

Community-acquired pneumonia (CAP) is the leading cause of mortality in children under 5 years of age globally. To improve the management of CAP, we must distinguish CAP from other common pediatric conditions and develop better diagnostic methods to detect the causative organism, so as to best direct appropriate resources in both industrialized and developing countries. Here, we review the diagnostic modalities available for identifying viruses and bacteria in the upper and lower respiratory tract of children, with a discussion of their utility and limitations in diagnosing CAP in children.


Asunto(s)
Bacterias/aislamiento & purificación , Infecciones Comunitarias Adquiridas/diagnóstico , Técnicas Microbiológicas/normas , Técnicas de Diagnóstico Molecular/normas , Neumonía/diagnóstico , Virus/aislamiento & purificación , Bacterias/genética , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/virología , Humanos , Técnicas Microbiológicas/tendencias , Técnicas de Diagnóstico Molecular/tendencias , Neumonía/microbiología , Neumonía/virología , Sistemas de Atención de Punto , Valor Predictivo de las Pruebas , Sistema Respiratorio/microbiología , Sistema Respiratorio/virología , Virus/genética
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