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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
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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In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.
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Infecções Meningocócicas , Adolescente , Adulto Jovem , Humanos , Austrália/epidemiologia , Inglaterra , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Países Baixos/epidemiologia , Vacinas CombinadasRESUMO
Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition, mainly affecting infants. In 2017, Argentina introduced a vaccination program against serogroups A, C, W and Y (MenACWY) for infants aged 3, 5 and 15 months and adolescents aged 11 years. The objective of this study was to review the burden of IMD in Argentina in 2010-2019. Data were obtained from national surveillance databases, and the study estimated IMD incidence, mortality, case-fatality rates, and serogroup distributions across age groups. A total of 1,972 IMD cases were reported in the study period, with the highest incidence in infants aged < 1 year. Incidence peaked in 2013 and subsequently declined. Mortality rates were 18 times higher in infants than in other age groups, reflecting the high impact of IMD in this age group. The case-fatality rate was 8.5% on average and increased with age. The proportion of notified cases with serogroup identification increased over the period, reaching 91% in 2019. The most common serogroups over the study period were serogroup B (48%) and serogroup W (42%), with an increase in B relative to W since 2015. In infants aged < 1 year, the proportion of serogroup B increased in recent years, reaching around 70% of characterized cases in 2018-2019. These results show the dynamism of IMD and indicate the importance of vaccination at an early age and offering protection against predominant serogroups. These data are valuable to support evidence-based decision-making in healthcare.
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Infecções Meningocócicas , Adolescente , Lactente , Humanos , Argentina/epidemiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Bases de Dados Factuais , Instalações de Saúde , Efeitos Psicossociais da DoençaRESUMO
INTRODUCTION: Invasive meningococcal disease (IMD) is a leading cause of life-threatening bacterial meningitis and septicemia. Evidence points to a knowledge gap among parents, teenagers, and healthcare providers (HCPs) regarding IMD and available vaccines, including those against the highly prevalent serogroup B. AREAS COVERED: An online survey was conducted between March 27 and 12 April 2019, to gather insights into the knowledge that parents/guardians have about IMD vaccines. The children were aged 2 months to 10 years in Australia, Brazil, Germany, Greece, Italy, and Spain, 5-20 years in the UK, and 16-23 years in the USA. The findings were discussed in the context of the available literature and solutions were proposed to minimize the knowledge gap and the barriers to vaccination against IMD. EXPERT OPINION: The survey demonstrated that parents have a good understanding of IMD but a limited understanding of the different serogroups and vaccines. The available literature highlighted multiple barriers to IMD vaccine uptake; these may be reduced through education of HCPs, clear recommendations to parents by HCPs, the use of technology, and disease-awareness initiatives that engage parents through physical and digital channels. Further studies are warranted to assess the impact of the COVID-19 pandemic on IMD vaccination.
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COVID-19 , Infecções Meningocócicas , Vacinas Meningocócicas , Criança , Adolescente , Humanos , Pandemias , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/microbiologia , Vacinação , SorogrupoRESUMO
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
Neisseria meningitidis, a bacterium that colonizes in the human nasopharynx, occasionally causes invasive meningococcal disease leading to meningitis or septicemia. Different serogroups and lineages (clonal complexes) are related to the occurrence and epidemiology of N. meningitidis. Despite vaccines for most serogroups, N. meningitidis lineages causing unusual clinical manifestations and a higher fatality rate compared to other lineages have been reported in South America. The present study focused on exploring the diversity of N. meningitidis prophages from South America and their relationship with the epidemiological variables of these strains. We found a high diversity of prophages among the different clonal complexes. By comparing them with previously described N. meningitidis phages and prophages, we revealed groups of prophages sharing similar compositions, which could be useful for prophage comparison in N. meningitidis. Furthermore, we observed a high correlation between the prophage content and epidemiological features, e.g., pathogenicity or clonal complex. Additionally, a distinctive filamentous prophage named here as IMSAR-11 (Invasive Meningococci from South America Related to cc11) was identified. Interestingly, two versions of IMSAR-11, circular and chromosomally integrated, were found. Overall, this study reinforces the importance of the genomic characterization of circulating N. meningitidis lineages to generate new targets for lineage monitoring, diagnosis, or appropriateness of vaccine development. Further studies are necessary to understand the role of these prophages in the persistence, dispersal, and virulence of N. meningitidis in the world.
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Infecções Meningocócicas , Neisseria meningitidis , Humanos , Neisseria meningitidis/genética , Prófagos/genética , Virulência/genética , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , SorogrupoRESUMO
Introducción: La meningitis puede ocurrir a cualquier edad y en individuos previamente sanos; concierne a la inflamación de las meninges por bacterias piógenas. La enfermedad meningocócica bacteriana prevalece en todo el mundo y constituye una emergencia médica con una alta morbilidad y mortalidad. Objetivo: Evaluar la sintomatología de la enfermedad meningocócica en Ecuador. Método: Se realizó una investigación de tipo cualicuantitativa, se llevó a cabo una revisión bibliográfica exhaustiva en buscadores bibliográficos con la búsqueda de palabras claves: enfermedad meningocócica por bacteria infecciosa. Se estudió el universo constituido por 151 pacientes afectados. Las variables edad en años de los afectados, factores de riesgo dependientes y síntomas presentes permitió a los autores plantear las conclusiones. Resultados: El 56,30 % de la población es de sexo masculino, con una edad promedio de aproximadamente 10 meses. El 63,58 % población de estudio es menor de 1 año de edad, la cantidad de síntomas presentados fue variable, del 11 % con 4 o más síntomas y el 47 % con un síntoma. La mala higiene en las personas se presentó en un 35,20 %. La sintomatología está relacionada con el consumo de caracoles y agua sin hervir. Conclusiones: La enfermedad meningocócica ocasiona daños a nivel del cerebro y medula espinal y su número de infecciones ha incrementado en los últimos años. La limpieza inadecuada de los alimentos supone un riesgo para adquirir la enfermedad. Los síntomas más frecuentes son: afectación neurológica, convulsiones, vómitos y náuseas, además la presencia de eosinófilos en sangre y líquido cefalorraquídeo.
Introduction: Meningitis can affect at any age and healthy individuals; it´s the inflammation of the meninges caused by the infection with pyogenic bacteria. Meningococcal disease is prevalent worldwide and constitutes a medical emergency with high morbidity and mortality. Objective: To assess the symptomatology of meningococcal disease in Ecuador. Method: A qualitative-quantitative research was carried out, an exhaustive bibliographic review was conducted in bibliographic search engines with the use of keywords: meningococcal disease caused by infectious bacteria. A total of 151 affected patients (as universe) were studied. The variables: age of those affected patients, dependent risk factors and symptoms present, helped in the authors final conclusions. Results: The 56.30% of the studied population was male, with an average age of approximately 10 months. The 63.58% of the studied population is under 1 year of age, the number of symptoms presented was variable, 11% with 4 or more symptoms and 47% with one symptom. Poor hygiene was presented in 35.20%. Symptomatology is related to the consumption of snails and unboiled water. Conclusions: Meningococcal disease causes damage to the brain and spinal cord, and infections has increased in recent years. Inadequate food sanitation is one of the risks for acquiring the disease. The most frequent symptoms are: neurological involvement, convulsions, vomiting and nausea, as well as the presence of eosinophils in blood and cerebrospinal fluid.
Introdução: A meningite pode ocorrer em qualquer idade e em indivíduos previamente saudáveis; diz respeito à inflamação das meninges por bactérias piogênicas. A doença meningocócica bacteriana é prevalente em todo o mundo e constitui uma emergência médica com alta morbidade e mortalidade. Objetivo: Avaliar os sintomas da doença meningocócica no Equador. Método: Realizou-se uma investigação quali-quantitativa, realizou-se uma revisão bibliográfica exaustiva em buscadores bibliográficos com a busca das palavras-chave: doença meningocócica por bactéria infecciosa. Foi estudado o universo constituído por 151 pacientes acometidos. As variáveis idade em anos dos afetados, fatores de risco dependentes e sintomas presentes permitiram aos autores tirar conclusões. Resultados: 56,30% da população é do sexo masculino, com idade média de aproximadamente 10 meses. 63,58% da população estudada é menor de 1 ano, o número de sintomas apresentados foi variável, 11% com 4 ou mais sintomas e 47% com um sintoma. A má higiene das pessoas foi apresentada em 35,20%. Os sintomas estão relacionados ao consumo de caracóis e água não fervida. Conclusões: A doença meningocócica causa danos ao cérebro e à medula espinhal e o número de infecções aumentou nos últimos anos. A limpeza inadequada dos alimentos representa um risco para a aquisição da doença. Os sintomas mais frequentes são: comprometimento neurológico, convulsões, vômitos e náuseas, além da presença de eosinófilos no sangue e líquido cefalorraquidiano.
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Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.
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COVID-19 , Meningite Meningocócica , Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Brasil/epidemiologia , Humanos , Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/epidemiologia , PandemiasRESUMO
Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition mainly affecting children and adolescents. Active surveillance between 2005 and 2016 at Tijuana General Hospital, Mexico, indicated that the incidence of IMD in Tijuana was higher than previously thought, at 2.69 per 100,000 population aged <16 years. The objective of this study was to estimate the economic burden associated with 51 IMD cases in children aged <16 years identified over the 11 years of active surveillance at Tijuana General Hospital, Mexico. Healthcare resource usage for the IMD cases was obtained from the hospital database and combined with unit costs from the hospital purchasing department or national databases to estimate total healthcare costs over a follow-up period of 3 months. Societal costs were represented by the value of lost wages for parents or guardians. All costs were expressed in US$. Over the 11-year study period there were 51 IMD cases, of which 13 (25%) were fatal. The total cost for all 51 cases over the 11-year study period was US$1,054,499 (average per case US$20,676), of which direct healthcare costs comprised US$1,029,948 (average per case US$20,195) and societal costs US$24,551 (average per case US$481). Extrapolated to the population of Tijuana region aged <16 years, the estimated annual economic burden of IMD was US$268,794. The major cost driver was the cost of hospitalization. These data illustrate the significant economic burden associated with IMD in Tijuana, and will be useful in assessing optimal vaccination programs against meningococcal disease in Mexico.
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Infecções Meningocócicas , Vacinas Meningocócicas , Criança , Adolescente , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Custos de Cuidados de Saúde , Vacinação , Hospitalização , Incidência , Vacinas Meningocócicas/uso terapêuticoRESUMO
Invasive meningococcal disease (IMD) can occur in travelers returning from mass-gathering events or endemic regions. We present a 60-year-old Argentine traveler to Tokyo who developed IMD by Neisseria meningitidis Serogroup W135 during her stay in Japan. N. meningitidis serogroup W135 infection has become common in Argentina, whereas IMD less commonly occurs in Japan. Considering the prevalence, the patient most likely acquired the infection in Argentina, and it developed in Japan. Air travel enables passengers to reach the four corners of the world within a few days. IMD should be considered in travelers due to its potential to induce rapid clinical deterioration and transmission.
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Infecções Meningocócicas , Neisseria meningitidis Sorogrupo W-135 , Neisseria meningitidis , Argentina/epidemiologia , Feminino , Humanos , Japão , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/epidemiologia , Pessoa de Meia-Idade , SorogrupoRESUMO
RESUMEN La enfermedad meningocócica representa un problema de salud pública y una de las principales causas de morbilidad y mortalidad en todo el mundo. Los serogrupos que causan la mayor carga de enfermedad a nivel global son A, B, C, W e Y. El objetivo del estudio fue describir los serogrupos y la resistencia antimicrobiana de Neisseria meningitidis aisladas de enfermedad invasiva en Paraguay durante el periodo 2010-2020. Se estudiaron todas las muestras de líquido cefalorraquídeo y sangre con aislamientos o detección de ADN por PCR de N. meningitidis de pacientes de diversas edades, que fueron remitidas al Laboratorio Central de Salud Pública durante el periodo 2010-2020, dentro del marco de la vigilancia epidemiológica de meningitis (n=163) en Paraguay. La mayor frecuencia de hallazgos de N. meningitidis se observó en el grupo de edad de < 1 año. El 25,7% de los casos correspondió al serogrupo B, el 52,1% al serogrupo C, 18,4% al serogrupo W y 3,7% al serogrupo Y. En el 2018, se evidenció la mayor cantidad de casos por serogrupo C (n=27). La menor frecuencia de sensibilidad disminuida a penicilina G fue en el 2010 (12,5%) y la mayor en el 2014 (100,0%). Se registró un aumento de casos por serogrupo C a partir del 2017, posicionándose como serogrupo prevalente hasta el 2020, y además, un aumento de la sensibilidad disminuida a la penicilina. La vigilancia es de importancia en el control de la enfermedad meningocócica para detección de brotes, estimación de la carga de enfermedad, análisis de resistencia antimicrobiana, distribución de serogrupos y evaluaciones de estrategias de control.
ABSTRACT Meningococcal disease represents a public health problem and one of the main causes of morbidity and mortality worldwide. The serogroups that cause the highest burden of disease globally are A, B, C, W, and Y. The aim of the study was to describe serogroups and antimicrobial resistance of Neisseria meningitidis isolated from invasive disease in Paraguay during the 2010-2020 period. Samples of cerebrospinal fluid and blood with isolates or detection of DNA by PCR of N. meningitidis from patients of different ages referred to the Central Public Health Laboratory during the period 2010-2020 within the framework of the epidemiological surveillance of meningitis (n = 163) in Paraguay were studied. The highest frequency of N. meningitidis findings was observed in the <1 year age group, 25.7% of the cases corresponded to serogroup B, 52.1% to serogroup C, 18.4% to serogroup W and 3.7% to serogroup Y. In 2018, the highest number of cases by serogroup C (n = 27) was found. The lowest frequency of decreased sensitivity to penicillin G was in 2010 (12.5%) and the highest in 2014 (100.0%). There was an increase in cases due to serogroup C in 2017, positioning itself as the prevalent serogroup until 2020, in addition, there was an increase in decreased sensitivity to penicillin. Surveillance is important in the control of meningococcal disease for outbreak detection, estimation of the burden of disease, analysis of antimicrobial resistance, serogroup distribution, and evaluations of control strategies.
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Invasive meningococcal disease (IMD) is a severe infection caused by Neisseria meningitidis, with mortality rates ranging from 10% to 40%. IMD has been confirmed to be an endemic disease in Tijuana, Mexico, right across the border from San Diego, California. To date, coronavirus disease 2019 (COVID-19) is the most severe pandemic, causing more than 5.5 million deaths globally. Prior or co-infections of influenza with IMD has been reported previously; however, the participation of other respiratory viruses facilitating the invasiveness of N. meningitidis is either not shown or remains unclear. Here, we report the case of an unvaccinated (for IMD and COVID-19) seven-year-old child who had confirmed fatal IMD caused by N. meningitidis, serogroup C, and was co-infected by severe acute respiratory syndrome coronavirus 2.
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BACKGROUND: A serogroup W (MenW) outbreak in Chile prompted a meningococcal vaccination campaign using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children since 2012, followed by its introduction into the National Immunization Program (NIP) in toddlers from 2014. Direct protection was observed, but no indirect effects in other age-groups were evidenced. The aim of this study was to describe invasive meningococcal disease (IMD) cases in Chile between 2009 and 2019, and its trend after the introduction of MCV-ACWYs. METHODS: IMD cases, cumulative incidence per 100,000 inhabitants, CFR, and vaccination uptake were described. Data were obtained from the Public Health Institute and NIP. RESULTS: Overall-IMD cases increased in 2009-2014 period, followed by a decline in 2015-2019, focused in infants, children <5 years and people ≥60 years. Serogroup B (MenB) and MenW alternate its predominance. Median overall incidence was 0.6/100,000, increasing from 0.6/100,000 in 2009 to 0.8/100,000 in 2014, later decreasing to 0.4/100,000 in 2019. Median incidences for MenB, serogroup C (MenC) and Y (MenY) were 0.25/100,000, <0.01/100,000 and <0.01/100,000, respectively. Median MenW incidence was 0.53/100,000, increasing from 0.01/100,000 in 2009 to 0.56/100,000 in 2014, followed by a constant decline to 0.12 in 2019. Infants, children <5 years and adults ≥60 years were affected the most, with median incidences of 9.7, 0.9 and 0.93, decreasing to 1.3, 0.1 and 0.1/100,000 in 2019, respectively. Median overall-CFR was 19%, 7.5% for MenB and 24.5% for MenW. Median MCV-ACWY uptake was 93% CONCLUSION: Overall-IMD, MenW cases and incidence declined since 2015 after the MCV-ACWY introduction, while MenB, MenC and MenY have been stable. MenW incidence declined in all age groups, including non-immunized infants and people >60 years. Further analysis and a longer period of observation are needed to have a more robust conclusion about this epidemiological trend. By 2019, CFR remains high.
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Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Adulto , Chile/epidemiologia , Humanos , Lactente , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Pessoa de Meia-Idade , Sorogrupo , Vacinas ConjugadasRESUMO
INTRODUCTION: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. METHODS: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. RESULTS: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. CONCLUSION: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.
Assuntos
Injúria Renal Aguda , Rim , Infecções Meningocócicas , Neisseria meningitidis/isolamento & purificação , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica/métodos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Interleucinas/análise , Rim/imunologia , Rim/microbiologia , Rim/patologia , Infecções Meningocócicas/complicações , Infecções Meningocócicas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Infiltração de Neutrófilos , Receptor 2 Toll-Like/análise , Receptor 4 Toll-Like/análise , Uromodulina/análiseRESUMO
Invasive meningococcal disease (IMD) is an uncommon yet unpredictable, severe, and life-threatening disease with the highest burden in young children. In Chile, most IMD is caused by meningococcal serogroup B (MenB) and W (MenW) infection. In response to a MenW outbreak in 2012, a toddler vaccination program was implemented using quadrivalent meningococcal conjugate vaccine against serogroups A, C, W and Y (MenACWY). The vaccine program, however, does not protect infants or other unvaccinated age groups and does not protect against MenB IMD. Since 2017, MenB IMD cases are becoming increasingly prevalent. Using a dynamic transmission model adapted for Chile, this analysis assessed the public health impact (reduction in IMD cases, long-term sequelae, deaths, and quality-adjusted life-years) of six alternative vaccination strategies using MenACWY and/or the four-component MenB (4CMenB) vaccine in infants, toddlers, and/or adolescents compared to the National Immunization Program (NIP) implemented in 2014. Strategies that added infant 4CMenB to MenACWY in toddlers or adolescents would prevent more IMD than the current NIP, observed within the first 5 years of the program. Replacing the NIP by an adolescent MenACWY strategy would prevent more IMD in the longer term, once herd immunity is established to protect unvaccinated infants or older age groups. The strategy that maximized reduction of IMD cases and associated sequelae in all age groups with immediate plus long-term benefits included infant 4CMenB and MenACWY in both toddlers and adolescents. This analysis can help policymakers determine the best strategy to control IMD in Chile and improve public health. A set of audio slides linked to this manuscript can be found at https://doi.org/10.6084/m9.figshare.16837543.
Plain Language Summary (PLS)What is the context?Invasive meningococcal disease (IMD) is a severe, sometimes fatal, unpredictable disease with highest rates in infants, young children, and adolescents. It is caused by different serogroups of Neisseria meningitidis bacteria. Most cases in Chile are due to meningococcal serogroups B (MenB) and W (MenW). Following a MenW IMD outbreak in 2012, vaccination was introduced, leading to the current National Immunization Program (NIP) in toddlers with quadrivalent meningococcal conjugate vaccine (MenACWY) (protecting against IMD caused by MenA, C, W, and Y).What is new?A disease model to predict the impact of vaccination strategies in the Chilean population compared six alternative strategies, using the multi-component MenB (4CMenB) vaccine for infants (protecting against MenB, with potential cross-protection against MenW and Y IMD) and/or the MenACWY vaccine for toddlers and/or adolescents.What is the impact?Results, compared to the NIP, show that: Strategy 1 (a program targeting only infants with 4CMenB) would reduce more MenB cases but fewer MenA, C, W and Y cases resulting in a lower reduction of total IMD cases in the long term; Strategy 3 (a program targeting only adolescents with MenACWY) would have a similar effect to the NIP in the short term but a far greater IMD reduction in the long term (as vaccinating this age group eventually reduces transmission to other age groups, reducing their risk of disease); all the other strategies targeted more than one age group, further reducing numbers of IMD cases compared with the NIP. The greatest benefits were seen with infant 4CMenB vaccination combined with toddler and adolescent MenACWY vaccination. Results can help policymakers determine the best IMD strategy to maximize the benefits of available meningococcal vaccines.
Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Adolescente , Idoso , Pré-Escolar , Chile/epidemiologia , Progressão da Doença , Humanos , Programas de Imunização , Lactente , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Saúde Pública , Vacinação , Vacinas ConjugadasRESUMO
INTRODUCTION: Meningococcal vaccines to protect against invasive meningococcal disease (IMD) vary in terms of vaccine technology and serogroup coverage (Polysaccharide MnACWY, conjugated C and ACWY, outer membrane vesicle-based or protein-based B vaccines), and the national recommendations for each of them vary in terms of target population and number of doses. We sought to understand factors associated with the evolution of meningococcal vaccination program recommendations in four countries with formal evaluation processes: the UK, US, the Netherlands, and Canada. AREAS COVERED: A targeted review of published literature and internet sources for the four countries relating to meningococcal vaccination decision-making was conducted. The review focused on the impact of cost-effectiveness analyses on vaccine policy decisions and the extent to which variation in incidence of IMD and its potential catastrophic consequences influenced policy decisions.The evolution of meningococcal vaccine recommendations in the four countries was mainly driven by changes in vaccine availability and changes in serogroup incidence. Public pressure due to the catastrophic nature of IMD influenced recommendations. The role of cost-effectiveness analyses varied across the 4 countries. EXPERT OPINION: The value of implementing meningococcal vaccination programs should be assessed using factors beyond those included in traditional cost-effectiveness analyses.
Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinação/métodos , Análise Custo-Benefício , Política de Saúde , Humanos , Programas de Imunização , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/economia , Vacinas Meningocócicas/imunologia , Formulação de Políticas , Vacinação/economia , Vacinas ConjugadasRESUMO
Asymptomatic carriers are a likely source of transmission of Neisseria meningitidis to close contacts who are placed at a higher risk for invasive meningococcal disease (IMD). Although N. meningitidis ciprofloxacin-resistance is rare, there have been an increase in the reports of resistant isolates mainly in patients diagnosed with IMD, and little is known about the N. meningitidis ciprofloxacin-resistance in the carrier populations. We performed a pharyngeal carriage study during a 2017 military setting outbreak in Peru, caused by a ciprofloxacin-resistant N. meningitidis B. The isolates analysed came from two hospitalized cases and six asymptomatic carriers. Whole-genome sequence-based analysis was performed and showed that strains carrying the Thr91Ile mutation, in the gene encoding for subunit A of DNA gyrase (gyrA), were responsible for the fluoroquinolone resistance (MICs ≥0.256 µg ml-1) and were closely related to highly virulent strains from France, Norway and the UK. Phylogenetic analysis of the gyrA gene revealed that likely these Peruvian isolates acquired resistance through horizontal gene transfer from Neisseria lactamica. Our study provides evidence for the emergence and propagation of ciprofloxacin-resistant N. meningitidis B from asymptomatic carriers, and recommends the introduction of serogroup B vaccines for high-risk populations.
Assuntos
Antibacterianos/farmacologia , Portador Sadio/microbiologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/isolamento & purificação , Portador Sadio/epidemiologia , Humanos , Infecções Meningocócicas/epidemiologia , Testes de Sensibilidade Microbiana , Neisseria meningitidis/classificação , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/genética , Peru/epidemiologia , FilogeniaRESUMO
BACKGROUND: Meningococcal disease (MD) presents a substantial public health problem in Brazil. Meningococcal C conjugate (MenC) vaccination was introduced into the routine infant immunization program in 2010, followed by adolescent vaccination in 2017. We evaluated changes in national and regional MD incidence and mortality between 2005 and 2018, serogroup distribution and vaccine coverage. METHODS: Data were obtained from national surveillance systems from 2005 to 2018. Age-stratified incidence and mortality rates were calculated and a descriptive time-series analysis was performed comparing rates in the pre-(2005-2009) and post-vaccination (2011-2018) periods; MD due to specific meningococcal serogroups were analyzed in the pre-(2007-2009) and post-vaccination (2011-2018) periods. RESULTS: From 2005 to 2018, 31,108 MD cases were reported with 6496 deaths; 35% of cases and deaths occurred in children < 5 years. Incidence and mortality rates declined steadily since 2012 in all age-strata, with significantly lower incidence and mortality in the post-vaccine introduction period in children aged < 1-year, 1-4 years, 5-9 years and 10-14 years. A significant decline in MenC disease in children < 5 years was observed following MenC vaccine introduction; infants < 1 year, from 3.30/100,000 (2007-2009) to 1.08/100,000 (2011-2018) and from 1.44/100,000 to 0.42/100,000 in 1-4-year-olds for these periods. Reductions in MenB disease was also observed. MenW remains an important cause of MD with 748 cases reported across 2005-2018. While initial infant vaccination coverage was high (>95% nationwide), this has since declined (to 83% in 2018); adolescent uptake was < 20% in 2017/18). Regional variations in outcomes and vaccine coverage were observed. CONCLUSION: A substantial decline in incidence and mortality rates due to MD was seen following MenC vaccine introduction in Brazil, especially among children < 5 years chiefly driven by reductions in MenC serogroup. While these benefits are considerable, the prevalence of MD due to other serogroups such as MenW and MenB remains a concern. A video summary linked to this article can be found on Figshare: https://doi.org/10.6084/m9.figshare.13379612.v1.
Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Humanos , Programas de Imunização , Incidência , Lactente , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , VacinaçãoRESUMO
BACKGROUND: Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed. METHODS: We conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017. RESULTS: Forty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3-4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules. CONCLUSIONS: MCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.