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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: 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
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
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.
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Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo C , Neisseria meningitidis , Adjuvantes Imunológicos , Hidróxido de Alumínio , Animais , Anticorpos Antibacterianos , Toxina da Cólera , Imunização , Imunoglobulina G , Memória Imunológica , Interleucina-17 , Interleucina-4 , Camundongos , Polissacarídeos , Porinas , SorogrupoRESUMO
En el presente trabajo se realiza la estandarización del procedimiento espectrofotométrico de determinación de polisacárido capsular e intermedios de Neisseria meningitidis serogrupo X, mediante la determinación de los grupos fosfodiéster presentes en su estructura, por el método de Chen. Se realizó un análisis de los siguientes criterios para la estandarización: linealidad, precisión (repetibilidad y precisión intermedia) y exactitud. Se demostró mediante el diseño experimental y los procedimientos estadísticos empleados que el método es lineal (r > 0,99), el coeficiente de variación del factor respuesta < 5 por ciento, la desviación estándar relativa de la pendiente < 2 por ciento, no existiendo diferencia estadísticamente significativa entre el intercepto de la ecuación con respecto a cero; exacto, porque no existe diferencia estadísticamente significativa entre la concentración determinada en un material de trabajo y su concentración nominal; también demostró ser repetible, pues el coeficiente de variación de las concentraciones de la muestra evaluada (2,44; 2,43; 0,88 por ciento para las concentraciones bajas, medias y altas, respectivamente) es inferior al 3 por ciento y no existen diferencias estadísticamente significativas entre las medias de los resultados obtenidos por dos analistas, evaluados durante cuatro días a tres niveles de concentración. La precisión intermedia es satisfactoria(AU)
The present work comprises the standardization a spectrophotometric procedure for assessing Neisseria meningitidis, serogroup X capsular polysaccharide and their intermediates of modification, the phosphodiesters groups present in its structure, based on Chen method. An analysis of the following standardization criteria was performed: linearity, precision (repeatability and intermediate precision) and accuracy. It was demonstrated through the experimental design and the statistical procedures used that the method is linear (r > 0.99), the coefficient of variation of the response factor < 5 percent, the relative standard deviation of the slope < 2 percent, with no statistically significant difference between the intercept of the equation with respect to zero; exact, because there is no statistically significant difference between the concentration determined in a work material and its nominal concentration; it also proved to be repeatable, because the coefficient of variation of the concentrations of the sample (2.44; 2.43; 0.88 percent for low, medium and high concentrations respectively) is less than 3 percent and there is no statistically significant difference between the means of the results obtained by two analysts, evaluated for four days at three concentration levels. Its intermediate precision was satisfactory(AU)
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Humanos , Masculino , Feminino , Padrões de Referência , Espectrofotometria/métodos , Fatores de Virulência , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/epidemiologia , Inibidores de FosfodiesteraseRESUMO
Resumen Neisseria meningitidis es una bacteria gramnegativa asociada frecuentemente a enfermedades invasoras de elevada mortalidad. Si bien su reservorio natural es la nasofaringe humana, en los últimos años han aumentado los aislamientos de este agente en la mucosa anorectal, principalmente en hombres que tienen sexo con hombres (HSH). Presentamos el caso de un HSH con infección por VIH, que consultó por un cuadro de uretritis y sifilis primaria, en el cual se aisló N. meningitidis en una muestra anorectal. Fue tratado en forma empírica con ceftriaxona y azitromicina, realizándose un cultivo de control post-tratamiento que fue negativo. A pesar del aumento de las infecciones y colonizaciones anogenitales por N. meningitidis, se desconoce su rol como patógeno genital, en la transmisión de otras infecciones y la necesidad de esquemas terapéuticos específicos.
Abstract Neisseria meningitidis is a Gram-negative bacterium frequently associated with invasive diseases with high mortality. Although its natural reservoir is the human nasopharynx, in recent years there have been increasing reports of isolation of this agent in the anorectal mucosa, mainly in men who have sex with men (MSM). We present the case of an HIV-positive MSM who consulted for urethritis and primary syphilis, in which N. meningitidis was isolated in an anorectal specimen. He was treated empirically with ceftriaxone and azithromycin, and a post-treatment control culture was negative. Despite the increase in anogenital infections and colonization by N. meningitidis, its role is unknown as a genital pathogen and in the transmission of other infections and the need for specific therapeutic regimens.
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Humanos , Masculino , Adulto , Homossexualidade Masculina , Neisseria meningitidis/isolamento & purificação , Ceftriaxona/uso terapêutico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Azitromicina , Minorias Sexuais e de Gênero , Infecções Meningocócicas/tratamento farmacológicoRESUMO
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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Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by Neisseria meningitidis serogroup W (MenW) strains.Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of N. meningitidis serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive N. meningitidis serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.Results. A predominance (58.5â%, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1-5, VR2-2, FetA 1-1, and a novel fHbp peptide 1241 was found on invasive N. meningitidis W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5â% (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8â%;4/27), 1 serogroup/genogroup Y isolate (3.7â%;1/27), 22 (81.5â%; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.
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Infecções Meningocócicas , Neisseria meningitidis , Adolescente , Brasil/epidemiologia , Estudos Transversais , Humanos , Infecções Meningocócicas/epidemiologia , Neisseria meningitidis/genética , SorogrupoRESUMO
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.
Assuntos
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
Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.
Assuntos
Artrite Infecciosa , Exantema , Infecções Meningocócicas , Neisseria meningitidis , Adulto , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/etiologia , Artrite Infecciosa/terapia , Oxalato de Cálcio/uso terapêutico , Humanos , Masculino , Infecções Meningocócicas/complicações , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/tratamento farmacológicoRESUMO
BACKGROUND Neisseria meningitidis strains belonging to clonal complex 11 is the cause of numerous outbreaks and epidemics in the United States, Canada and Europe, accounting for 49.5% of cases of meningococcal disease caused by serogroup C worldwide. In Brazil, it is the second most frequent clonal complex within this serogroup. The genetic characterisation of cc11/ET-15 variants is important for the epidemiological monitoring of meningococcal disease, through the identification of circulating epidemic clones, to support specific actions of Health Surveillance aiming outbreaks control. OBJECTIVES The objective of this study was to identify features in the genome of cc11/ET-15 clones through whole-genome sequencing (WGS), that differ from cc11/non-ET-15 strains that could explain their virulence. METHODS The whole genome of three cc11/ET-15 representative strains were sequenced with a minimum coverage of 100X with the MiSeq System and compared to the genome of cc11/non-ET-15 strains. RESULTS Genome analysis of cc11/ET-15 variants showed the presence of resistance factors, mobile genetic elements and virulence factors not found in cc11/non-ET-15 strains. MAIN CONCLUSIONS Our results show that these strains carry virulence factors not identified in cc11/non-ET-15 strains, which could explain the high lethality rates attributed to this clone worldwide.
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BACKGROUND: Primary meningococcal arthritis (PMA) is defined as the presence of acute septic arthritis with the identification of Neisseria meningitidis in synovial fluid or blood cultures but no clinical evidence of sepsis or meningitis. This report aimed to describe a clinical case of PMA caused by serogroup W, an uncommon etiology of this disease in Uruguay, and review the available literature. CASE REPORT: We report the case of a 5-year-old female, with no past medical history, admitted to the emergency department with a 12-hour history of fever of 39 °C and a limp. The patient was hemodynamically stable and had no clinical evidence of meningitis. Hip ultrasound showed an increase in synovial fluid. Arthrocentesis showed purulent exudate and synovial fluid culture showed no growth after five days. The blood culture showed isolates of N. meningitidis, serogroup W. The patient received treatment with ceftriaxone, and drainage of the affected joint was performed with excellent clinical response. CONCLUSIONS: Primary meningococcal arthritis is a rare presentation of meningococcal disease. Systematic arthrocentesis and the adequacy of antibiotic therapy when septic arthritis is clinically suspected are essential for confirming the diagnosis and decompressive drainage of the involved joint. This report is the first of PMA caused by serogroup W in Uruguay. Although the most common serogroup involved in meningococcal arthritis is serogroup B in Uruguay, an increase in serogroup W-related diseases has been reported in Chile and Argentina, emphasizing the need for epidemiological surveillance.
Assuntos
Artrite Infecciosa , Infecções Meningocócicas , Neisseria meningitidis , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Ceftriaxona , Criança , Pré-Escolar , Feminino , Humanos , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/tratamento farmacológico , SorogrupoRESUMO
PURPOSE: In the present study, meningococcal serogroup B outer membrane vesicles (OMVs) were associated with bilayer fragments of a cationic lipid, dioctadecyldimethylammonium (DDA-BF), used as adjuvant, in an antigenic preparation tested in adult female outbred mice. This adjuvant was compared to the traditional adjuvant aluminum hydroxide. MATERIALS AND METHODS: The potential in generating humoral response was evaluated by enzyme-linked immunosorbent assay (ELISA). Individual serum was collected and immunoglobulin G (IgG), IgG1, IgG2a, and IgG2b were quantified. Analyses were carried out 15 and 60 days after immunization. Antibodies avidity index were also analyzed by ELISA. Immunoblot and dot-ELISA were carried out to evaluate specific reaction for homologous strains and cross-reactive antigens present in other meningococcal strains isolated in 2011-2012 year, in Brazil. Delayed type hypersensitivity was used as indicative of cellular immunity and compared between two experimental groups, 24 hours after homologous strain challenge. RESULTS: The OMVs of Neisseria meningitidis, and N. lactamica (related species) were characterized by electrophoretic separation of proteins in 13% polyacrylamide gel. The strains presented antigens in the range of 8 to 130 kDa, showing a heterogeneous protein migration pattern. In the group immunized with OMVs/DDA-BF, we found no significant production of total IgG 15 days after the first immunization. On the other hand, 60 days after first immunization both adjuvants act benefiting total IgG production similarly. The antibodies of the IgG isotype produced by animals immunized after one or two doses after first immunization, showed intermediate and high avidity, independent on the adjuvant used. In both experimental groups the swelling of the footpads was significantly higher than those of the controls, suggesting that only one dose was enough to stimulate the generation of cellular immunity. CONCLUSION: The use of this cationic adjuvant for N. meningitidis OMVs preparation revealed good potential for future new antigen preparation for N. meningitidis vaccine.
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INTRODUCTION: Vaccination is an effective strategy to combat invasive meningococcal disease (IMD). Vaccines against the major disease-causing meningococcal serogroups are available; however, development of vaccines against serogroup B faced particular challenges, including the inability to target traditional meningococcal antigens (i.e. polysaccharide capsule) and limited alternative antigens due to serogroup B strain diversity. Two different recombinant, protein-based, serogroup B (MenB) vaccines that may address these challenges are currently available. These vaccines have been extensively evaluated in pre-licensure safety and immunogenicity trials, and recently in real-world studies on effectiveness, safety, and impact on disease burden. AREAS COVERED: This review provides healthcare professionals, particularly pediatricians, an overview of currently available MenB vaccines, including development strategies and evaluation of coverage. EXPERT OPINION: Overall, recombinant MenB vaccines are valuable tools for healthcare professionals to protect patients against IMD. Their development required innovative design approaches that overcame challenging hurdles and identified novel protein antigen targets; however, important distinctions in the approaches used in their development, evaluation, and administration exist and many unanswered questions remain. Healthcare providers frequently prescribing MenB vaccines are challenged to keep abreast of these differences to ensure patient protection against this serious disease.