Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage.

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 (58.5 %, 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 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 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.

Invasive meningococcal disease in Chile seven years after ACWY conjugate vaccine introduction.

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.

Trajectory of serogroups causing Invasive Meningococcal Disease in Santa Catarina state, Brazil (2007-2019)

Abstract The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.

Trajectory of serogroups causing Invasive Meningococcal Disease in Santa Catarina state, Brazil (2007-2019).

The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.

Meningococcal invasive disease by serogroup W and use of ACWY conjugate vaccines as control strategy in Chile.

BACKGROUND: Serogroup causing invasive meningococcal disease (IMD) can change abruptly, as it occurred in Chile when serogroup predominance switched from MenB to MenW in 2012. As a response, a national vaccination strategy was implemented since 2012 using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children 9 months through 4 years of age. The aim of this study was to describe IMD cases by MenW in Chile 2009-2016, and to analyse its trend after the introduction of MCV-ACWY. METHODS: Descriptive study of IMD cases in Chile, period 2009-2016. Cumulative incidence and mortality rate per 100,000 inhabitants, and case fatality rate (CRF) were used for descriptive analysis. Linear regression was used for post-intervention trend analysis. RESULTS: In 2012, MenW, mainly ST-11 cc, became predominant. MenW incidence rose from 0.01/100,000 inhabitants in 2009 to a maximum of 0.6/100,000 in 2015. Infants and adults 80 years of age and older were mostly affected, with an incidence peak of 9.7/100,000 and 1.6/100,000, respectively, in 2015. In the group of children from 1 to 4 years of age MenW incidence declined from 1.3/100,000 in 2012 to 0.1/100,000 in 2016, a 92.3% reduction after vaccination implementation. In the same period and age-cohort, CFR decreased from 23% to 0%. High mortality rates concentrated in infants and adults 80 years of age and over. CONCLUSION: MenW became predominant in Chile since 2012. IMD cases increased steadily from 2009 to 2016, with higher incidence, CFR and mortality concentrating in infants and people 80 years of age and older. MCV-ACWY provided direct protection against MenW, reducing its incidence after mass meningococcal vaccine implementation. Indirect effects of vaccination are not yet observed.

Plan de acción nacional frente a la emergencia de la cepa W-135 responsable de enfermedad meningocócica invasora en Chile, 2012-2013 / National action plan for the emergence of invasive meningococcal disease in Chile, 2012-2013

Invasive meningococcal disease is challenging for public health, mainly when it manifests with sudden changes in incidence, serogroups and hypervirulent clones that spread in the population, causing great alarm due to its sequelae and often fatal course, a situation that occurred in Chile, starting at week 26 of the year 2012. To face this scenario, an organization of multidisciplinary teams was required, called W-135 Action Plan in Chile, which included sanitary alerts, education, reinforcement of the epidemiological surveillance of suspicious cases, immediate diagnosis through state-of-the-art techniques, blocking of contacts, communication plans, and, from the 42nd week, ON the vaccination campaign was started for children aged from 9-months-old to less than 5 years of age. The vaccination strategy had a great impact on the decrease in incidence (1.3 to 0.1/100,000) and case fatality rate in the vaccinated population (23% to 0%), with a high safety profile, leading to its subsequent inclusion in the national immunization program. The ability to develop molecular, clinical and epidemiological studies allowed us to better understand the situation, supporting public health policy decisions for its control. The W-135 Action Plan implemented by the Ministry of Health in Chile, to manage the outbreak of meningococcal disease by Neisseria meningitidis serogroup W, demonstrated that the coordination of these efforts, through an organized Action Plan, allows the implementation of campaigns at the national level achieving high coverage of risk populations in short periods of time, generating a positive impact on the health of the population.

The current situation of meningococcal disease in Latin America and updated Global Meningococcal Initiative (GMI) recommendations.

The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate formulations (wherever possible), monitoring and evaluating implemented vaccination strategies, conducting cost-effectiveness studies, and developing specific recommendations for vaccination of high-risk groups.

Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage.

OBJECTIVES: Neisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000-2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution. METHODS: Representatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks. RESULTS: MenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the 'Hajj outbreak' strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct. CONCLUSIONS: High resolution 'genomic' multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally.

Evolving meningococcal immunization strategies.

Meningococcal disease is a major public health problem and immunization is considered the best strategy for prevention. The introduction of meningococcal C conjugate immunization schedules that targeted adolescents, with catch-up programs in several European countries, Australia and Canada proved to be highly effective, with dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals. Meningococcal quadrivalent (A, C, W, Y) conjugate vaccines are now licensed and are being used in adolescent programs in North America and to control serogroup W disease in South America. In the African meningitis belt, a mass immunization campaign against serogroup A disease using a meningococcal A conjugate vaccine is now controlling the devastating epidemics of meningococcal disease. After introducing new immunization programs, it is of importance to maintain enhanced surveillance for a better understanding of the changing nature of disease epidemiology. This information is crucial for identifying optimal immunization policies.

Vigilancia de laboratorio de enfermedad meningocóccica invasora en Chile, 2006-2012 / Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012

Background: Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. Aim: To show the results of this surveillance from 2006 to 2012. Methods: A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. Results: From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). Conclusions: Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

Introducción: La vigilancia de laboratorio de enfermedad meningocócica invasora (EMI) que realiza el Instituto de Salud Pública de Chile, confirma, seroagrupa y estudia el perfil genético de las cepas de Neisseria meningitidis provenientes de los laboratorios del país. Objetivo: En este artículo se muestra los resultados de esta vigilancia entre los años 2006 a 2012. Materiales y Métodos: Se realizó un análisis descriptivo de los casos confirmados de EMI, caracterización serológica, el análisis de susceptibilidad antimicrobiana y el estudio de subtipo genético de la cepa. El análisis se desagregó por serogrupo, edad y región. Resultados: En el período 2006-2012 fue confirmado un total de 486 cepas de N. meningitidis. A partir del año 2011 se observó un alza en la tasa de EMI dado por el número de casos del serogrupo W, afectando principalmente a niños bajo 5 años de edad. El W se transformó en el serogrupo prevalente el año 2012 (58,3%), desplazando al serogrupo B, el cual históricamente había sido prevalente. Predominaron principalmente las cepas pertenecientes al complejo clonal ST-32 complex/ET-5 complex (40,4% de las muestras) y el ST-41/44 complex/Lineage 3 (45,9% de las muestras). Conclusiones: El sistema de vigilancia de laboratorio ha permitido la identificación del serogrupo W, emergente en Chile. Esta información nos ha obligado a estar en permanente alerta y monitoreo de casos diarios, mediante la participación activa de todos los laboratorios clínicos del país.

Emergencia de la cepa W135 causante de enfermedad meningocócica invasora en Chile 2012 / Emergence of W135 meningococcal serogroup in Chile during 2012

The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile has changed. At the end of 2011, the W135 serogroup belonging to the hypervirulent clone ST-11 emerged. It affected diverse countries of the world, after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants, which is 30% higher than expected. Eighty eight percent of cases were confirmed by the National Reference Laboratory at the Chilean Public Health Institute. The serogroup was determined in 103 strains and 58% belonged to the W135 serogroup, surpassing for the first time the B serogroup (37%). The Metropolitan Region concentrated 80% of these cases, and the remaining 20% affected other seven regions of the country. Forty seven percent of cases corresponded to children less than 5 years of age. The predominant clinical presentation of the W135 serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was 27%, the highest in the past 20 years. With this information, the Chilean Ministry of Health decreed a sanitary alert and implemented an integrated approach to control and prevent W-135 IDM, denominated "W-135 Action Plan".

Caracterización clínica de los casos de enfermedad meningocóccica por serogrupo W135 confirmados durante el año 2012 en Chile / Clinical characterization of cases with meningococcal disease by W135 group in Chile, 2012

Background: During 2012 in Chile, there were 60 cases of serogroup W135 meningococcal disease, which accounts for 57.7% of identified serogroup cases. Aim: To describe main clinical features of patients with serogroup W135 meningococcal disease confirmed in 2012. Material and Methods: Descriptive study of case series based on retrospective review of medical records. Results: Male patients represented 61.7% and 46.7% were children under 5 years. At first clinical attention, 3.4% of patients were suspected of meningococcal disease, while 83.3% had meningococcemia as final diagnosis. Also at first attention, the most common symptoms or clinical signs were fever ≥ 38.0° C (60.3%), cold symptoms (52.5%), and nausea or vomiting (46.7%). Meningeal signs had a low frequency (8.7%). Diarrhea was the second most common symptom found among deceased patients (55.6%) and statistically higher than survivors (26.8%; p = 0.034). Six cases reported with sequelae: limb amputation, hearing loss or neurological damage, and mortality was 31.7%. Discussion: In 2012, serogroup W135 meningococcal disease reported high mortality, atypical clinical presentation, low initial meningococcal disease diagnosis, and a high number of cases with poor clinical course.

Introducción: En el año 2012 en Chile, se presentaron 60 casos de enfermedad meningocóccica (EM) causadas por serogrupo W135, que representa 57,7% de los casos seroagrupables. Objetivo: Describir las características clínicas de los casos de EM por serogrupo W135 confirmados durante el año 2012. Material y Métodos: Estudio descriptivo, de series de casos basada en la revisión de las fichas clínicas. Resultados: El 61,7% de los casos fueron varones y 46,7% tenía menos de 5 años. En la primera consulta, 3,4% tuvo sospecha de EM, en tanto 83,3% tuvo diagnóstico final de meningococcemia. En la primera consulta, los síntomas y/o signos más frecuentes fueron fiebre ≥ 38,0°C (60,3%), cuadro catarral respiratorio (52,5%) y náuseas y/o vómitos (46,7%). Mientras que los signos de irritación meníngea se presentaron en 8,7%. En los fallecidos la diarrea fue el segundo síntoma más frecuente (55,6%), y estadísticamente superior respecto de los sobrevivientes (26,8%; p = 0,034). Seis casos presentaron secuelas: amputaciones de extremidades, hipoacusia o daño neurológico y la letalidad fue de 31,7%. Discusión: la EM por el serogrupo W135 en el año 2012, tuvo una elevada letalidad, presentación clínica inespecífica, sospecha diagnóstica inicial baja y un alto número de casos cursaron con una mala evolución.

Recognition of the epidemiological significance of Neisseria meningitidis capsular serogroup W135 in the Rio de Janeiro region, Brazil

Neisseria meningitidis retains its ability to cause endemic and hiperendemic disease in human population living in any environment, as well as localized outbreaks and massive epidemics in civilians and military personnel. In Rio de Janeiro it has been reported in the 1990s as prolonged outbreak of serogroup B and at least one epidemic of serogroup C was well defined, both demanding quick action by the Public Health authorities. We report here the emergence of serogroup W135 meningococcal disease causing endemic and case cluster in Rio de Janeiro during the first years of this new century.