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Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.
The most common clinical manifestations of invasive meningococcal disease include meningitis and septicemia, which can be deadly, and many survivors suffer long-term serious after-effects. Most cases of invasive meningococcal disease are caused by six meningococcal serogroups (types), including serogroup B. Although vaccines are available against meningococcal serogroup B infection, these vaccines target antigens that are highly diverse. Consequently, the effectiveness of vaccination may vary from country to country because the meningococcal serogroup B strains circulating in particular regions carry different forms of the target vaccine antigens. This means it is important to test serogroup B strains isolated from specific populations to estimate the percentage of strains that a vaccine is likely to be effective against (known as 'vaccine strain coverage'). The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict strain coverage by the four-component meningococcal serogroup B vaccine, 4CMenB, against large numbers of serogroup B strains. In this study, we analyzed 284 invasive meningococcal serogroup B isolates collected between 2010 and 2014 in Argentina. Genetic analyses showed that the vaccine antigens of the isolates were diverse and some genetic characteristics had not been found in isolates from other countries. However, vaccine strain coverage estimated by gMATS was consistent with that reported in other parts of the world and with strain coverage results obtained for a subset via another method, the human serum bactericidal antibody (hSBA) assay. These results highlight the need for continued monitoring of circulating bacterial strains to assess the estimated strain coverage of meningococcal serogroup B vaccines.
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Antígenos de Bactérias , Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo B , Humanos , Argentina/epidemiologia , Vacinas Meningocócicas/imunologia , Vacinas Meningocócicas/administração & dosagem , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/epidemiologia , Lactente , Adolescente , Criança , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Pré-Escolar , Adulto Jovem , Neisseria meningitidis Sorogrupo B/genética , Neisseria meningitidis Sorogrupo B/isolamento & purificação , Neisseria meningitidis Sorogrupo B/imunologia , Adulto , Feminino , Masculino , Sequenciamento Completo do Genoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Genótipo , Adesinas Bacterianas/genética , Adesinas Bacterianas/imunologia , Pessoa de Meia-Idade , Porinas/genética , Porinas/imunologia , Ensaios de Anticorpos Bactericidas Séricos , Idoso , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/classificaçãoRESUMO
Purpose of Review: Despite the availability of effective vaccines against the three primary pathogens (Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries. Recent Findings: Bacterial meningitis represents a significant public health challenge for national and global health systems. Since vaccine-preventable meningitis remains highly prevalent in low-income and middle-income countries, the World Health Organization (WHO) recently developed a global roadmap to defeating meningitis by 2030 and ameliorating its associated neurological sequelae. Summary: There is a need for a global approach to surveillance and prevention of bacterial meningitis. Increasing vaccination coverage with conjugate vaccines against pneumococcus and meningococcus with optimal immunization schedules are high-value healthcare interventions. Additionally, overcoming diagnostic challenges and the early institution of empirical antibiotic therapy and, when feasible, adjunctive steroid therapy constitutes the pillars of reducing the disease burden of bacterial meningitis in resource-limited settings.
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COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.
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Anticorpos Antivirais , COVID-19 , Imunoglobulina G , Neisseria meningitidis , SARS-CoV-2 , Animais , Camundongos , Imunoglobulina G/sangue , Neisseria meningitidis/imunologia , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos BALB C , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adjuvantes de Vacinas/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/imunologia , Imunização/métodos , Afinidade de Anticorpos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Vacinas Meningocócicas/imunologia , Vacinas Meningocócicas/administração & dosagem , Memória Imunológica , Células Th1/imunologiaRESUMO
Surveillance of meningococcal disease (MD) is crucial after the implementation of vaccination strategies to monitor their impact on disease burden. Adolescent vaccination could provide direct and indirect protection. Argentina, Brazil, and Chile have introduced meningococcal conjugate vaccines (MCV) into their National Immunization Programs (NIP), while Uruguay has not. Here, we analyze the epidemiology of MD and vaccination experience from these four South American countries to identify needs and plans to improve the current vaccination programs. METHODOLOGY: Descriptive study of MD incidence rates, serogroup distribution, case fatality rates (CFR), and MCV uptakes during the period 2010-2021 in Argentina, Brazil, Chile, and Uruguay. Data were extracted from national surveillance programs, reference laboratories, NIPs, and Pubmed. RESULTS: MD overall incidence from 2010 to 2021 have a decreasing trend in Argentina (0.37 [IQR = 0.20-0.61]), Brazil (0.59 [IQR = 0.54-1.22]), and Chile (0.45 [IQR = 0.40-0.77]), while a significant increase in Uruguay (0.47 [IQR = 0.33-0.69]) was found from 2016 to 2019. During the COVID-19 pandemic, all countries sharply reduced their MD incidence. The highest incidence rates were observed among infants, followed by children 1-4 years of age. No second peak was evident in adolescents. A reduction in serogroup C, W, and Y cases has occurred in Argentina, Brazil, and Chile after introduction of MCV, serogroup B becoming predominant in all four countries. Median CFR was 9.0%, 21%, 19.9%, and 17.9% in Argentina, Brazil, Chile, and Uruguay, respectively. Median uptake of MCV for Argentina and Brazil were 66.6% and 91.0% for priming in infants; 54.7% and 84.5% for booster in toddlers; and 47.5% and 53% for adolescents; while for Chile, 95.6% for toddlers. CONCLUSIONS: Experience after the implementation of MCV programs in South America was successful, reducing the burden of MD due to the vaccine serogroups. High vaccine uptake and the inclusion of adolescents will be crucial in the post-pandemic period to maintain the protection of the population. The increase in the proportion of serogroup B cases emphasizes the importance of continuous surveillance to guide future vaccination strategies.
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INTRODUCTION: Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is associated with high morbidity and mortality. The aim of the current study was to describe the historical and recent epidemiology of IMD in Colombia. METHODS: This retrospective surveillance database analysis examined all available data on IMD in Colombia. Data were extracted from publicly available disease event reports and laboratory surveillance reports or obtained directly from hospitals in Cartagena. RESULTS: During 2015-2021, the overall incidence of IMD was 0.04-0.18 per 100,000 based on laboratory surveillance reports. IMD incidence was highest among infants aged < 1 year (0.52-1.47 per 100,000), as was IMD mortality (0.00-0.65 per 100,000). Serogroup B was the dominant serogroup responsible for IMD in Colombia during 1988-2014, but, since 2015, serogroup C has been dominant in all age groups, followed by serogroups B and Y. During 2010-2021 combined, the majority of IMD cases were reported in Bogotá (31.9%) and Antioquia (21.7%). Of 42 IMD cases in the city of Cartagena, 54.8% occurred in people who lived in the poorest neighborhoods, and these patients had the highest IMD lethality (52.2%) and the shortest median hospitalization duration (3 days). CONCLUSION: The overall incidence of IMD in Colombia was low but was highest among infants aged < 1 year. IMD cases tended to be concentrated in the more densely populated areas and in poorer neighborhoods. As the majority of IMD cases in Colombia since 2015 have been serogroup C, followed by B or Y, vaccination to protect against these serogroups could potentially be beneficial and help to achieve the World Health Organization's and Pan American Health Organization's roadmaps to defeat meningitis by 2030.
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Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is a public health problem, associated with high levels of morbidity and mortality, capable of causing outbreaks or epidemics, but preventable through vaccination. In Brazil, the main serogroups isolated are C and B. The last epidemic occurred in the '80s, in São Paulo, because of a B:4:P1.15 strain. Adult Swiss mice were immunized with outer membrane vesicles (OMV) of N. meningitidis strain C:4:P1.15, adjuvanted by the cationic lipid dioctadecyldimethylammonium bromide in bilayer fragments (DDA-BF), administered via prime-booster (intranasal/subcutaneous) scheme. The humoral response was assessed by Immunoblotting and ELISA, using homologous immunization strain and a different serogroup but equal serosubtype strain, N. meningitidis B:4:P1.15. Immunoblotting revealed the recognition of antigens associated with the molecular weight of Porin A and Opacity proteins, which are immunogenic but highly heterogeneous, and Tbp and NspA, which are more homogeneous between meningococci strains. ELISA results showed antibody production that persisted after 190 days and recognized the C:4:P1.15 and the B:4:P1.15 strains, with high avidity index. The adjuvanted group recognized antigens following the IN prime and had a higher avidity index against the heterologous strain. DDA-BF improved the humoral response, but the OMV alone induced high avidity index antibodies as well. Even though these are preliminary results, we see it as a promising approach for affordable meningococcal immunization in developing countries, at outbreak or epidemic situations. (AU)
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Brometos , Imunização , Reações Cruzadas , Meningite Meningocócica , Neisseria meningitidisRESUMO
INTRODUCTION: Invasive meningococcal disease (IMD) is a major health problem. Given the post-COVID-19 pandemic scenario with the loosening of the non-pharmacological measures to control the virus transmission and considering the observed global reduction of meningococcal vaccination coverage, an increase in IMD cases can be expected. METHODOLOGY: Using whole-genome sequencing, we characterized six Neisseria meningitidis serogroup X (MenX) isolates recovered from IMD cases in Brazil in the last 30 years. RESULTS: The predominance (66.6%, 4/6) of ST2888 presenting fHbp 160, NHBA 129, NadA 21, and PorA 19,15 was found on isolates. Two novel STs, 15458 and 15477, were described. CONCLUSION: This study describes the circulation of MenX lineage ST2888 in Brazil, previously reported only in Europe. Continuous universal surveillance is crucial to implement prompt public health measures aiming to prevent and control non-vaccine preventable serogroup X IMD cases.
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COVID-19 , Infecções Meningocócicas , Neisseria meningitidis Sorogrupo B , Neisseria meningitidis , Humanos , Antígenos de Bactérias/genética , Brasil/epidemiologia , Pandemias , Neisseria meningitidis Sorogrupo B/genética , COVID-19/epidemiologia , Neisseria meningitidis/genética , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/microbiologia , GenômicaRESUMO
INTRODUCTION: Neisseria meningitidis is associated with invasive infections causing high mortality rates. The objective of this study was to describe the population structure of Colombian invasive isolates with ST-9493, a potentially emerging clonal group in the country. METHODS: The complete genomes of 34 invasive isolates of serogroup B with ST-9493 and its variants at one or two loci were sequenced by Illumina to describe the phenotypic and genotypic characteristics of these isolates. RESULTS: The relationship of a clonal group associated with ST-136 CC41/44 was phylogenetically established, identifying two main clades composed of isolates from an outbreak or endemic. The most frequent alleles and peptides included porA 17, porB 44, fHbp 2.24, NHBA 10, and the FetA F5-17 variant. Most of the isolates were susceptible to the antibiotics evaluated. CONCLUSION: This study shows that meningococcal isolates with ST-9493 are an autochthonous clonal group with population dynamics and the capacity to cause endemic and epidemic meningococcal disease in Colombia.
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Infecções Meningocócicas , Neisseria meningitidis , Humanos , Neisseria meningitidis/genética , Colômbia/epidemiologia , Infecções Meningocócicas/epidemiologia , Sorogrupo , GenótipoRESUMO
Bacterial meningitis is one of the diseases that, despite the introduction of several vaccines, remains a serious public health concern. Streptococcus pneumoniae (Spn), Neisseria meningitidis (Nm), and Haemophilus influenzae (Hi) are responsible for most cases diagnosed in children, adolescents, and adult population. Rapid, sensitive, and specific laboratory assays are critical for effective diagnosis and treatment, particularly in countries like Mexico in which culture positivity rates are very low due to the use of antibiotics prior to sample collection and to delay in transporting samples to the laboratory. The aim of this study was to evaluate the use of real-time polymerase chain reaction (RT-PCR) of cerebrospinal fluid (CSF) as a rapid diagnostic test for bacterial meningitis and compare these results with bacterial culture in three general hospitals in Mexico. During a 5-year period (2014-2018), a total of 512 CSF samples obtained from patients in whom infectious meningitis was suspected as initial clinical diagnosis were tested with RT-PCR with species-specific targets for the three pathogens. For Spn, 5.07% samples were RT-PCR positive; 0.39% for Nm and none for Hi. Only five RT-PCR Spn positive samples had a positive culture. Sensitivity and specificity estimates for RT-PCR are 100% and 95.46%, respectively. DNA amplification methods can provide better sensitive diagnostic tests than the reference standard, which is culture, particularly when antimicrobial treatment is initiated before clinical samples can be obtained.
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Meningites Bacterianas , Neisseria meningitidis , Criança , Adulto , Adolescente , Humanos , Neisseria meningitidis/genética , Streptococcus pneumoniae/genética , Haemophilus influenzae/genética , Reação em Cadeia da Polimerase em Tempo Real , Meningites Bacterianas/diagnóstico , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Immunization is the key to prevent invasive meningococcal disease (IMD), caused by Neisseria meningitidis. Outer membrane vesicles (OMVs) can be used as meningococcal antigens. METHODS: Isogenic mice A/Sn (H2a) were immunized with low antigenic doses of OMVs of an N. meningitidis C:2a:P1.5 strain, via intranasal/intramuscular route, adjuvanted by cholera toxin subunit B (CTB) or via intramuscular route only, adjuvanted by aluminium hydroxide (AH). Mice were followed until old age and humoral and cellular responses were assessed by ELISA, Immunoblotting, Dot-blot, Serum-bactericidal assay, Immunohistochemistry and ELISpot. RESULTS: OMV+CTB and OMV+AH groups presented statistically higher antibodies titers, which persisted until middle and old ages. IgG isotypes point to a Th2 type of response. Avidity indexes were considered high, regardless of adjuvant use, but only groups immunized with OMVs and adjuvants (OMV+CTB and OMV+AH) presented bactericidal activity. The antibodies recognized antigens of molecular weights attributed to porin and cross-reactivity proteins. Although the spleen of old mice did not present differences in immunohistochemistry marking of CD68+, CD4+, CD79+ and CD25+ cells, splenocytes of immune groups secreted IL-4 and IL-17 when stimulated with OMVs and meningococcal C polysaccharide. CONCLUSION: We concluded that both adjuvants, CTB and AH, improved the immunogenicity of low doses of OMVs and contributed to a persistent immune response. Even though AH is well established in the vaccinology area, CTB seems to be a promising adjuvant candidate for meningococcal vaccines: it is suitable for mucosal delivery and supports a Th2 type of response. Therefore, OMVs are still a relevant vaccine platform.