The meningitis outbreak returns to Niger: Concern, efforts, challenges, and recommendations.

Meningitis, a disease that commonly manifests in African meningitis belt, continues to be a public health problem as it is a fatal disease that leave survivors with long-term effects. Most cases of meningitis are due to bacterial and viral infection, although parasites, fungus, cancer, drugs, and immune disorders can rarely cause meningitis. Stiff neck, high temperature, light sensitivity, disorientation, headaches, and vomiting are the most typical symptoms of meningitis. Niger, being in African meningitis belt, has been affected by many meningitis outbreaks. Since 2015, a total of 20,789 cases and 1369 fatalities (CFR 6.6%) have been documented in Niger. In contrast to earlier seasons, the current outbreak of meningitis in Niger exhibits both an increase in the number of cases and a rise in the growth rate. A total of 559 cases of meningitis, including 18 fatalities (overall CFR 3.2%), were reported in the Zinder Region, southeast of Niger, from 1 November 2022 to 27 January 2023, compared to 231 cases reported from 1 November 2021 to 31 January 2022. In the current outbreak, the Neisseria meningitidis serogroup C (NmC) is responsible for the majority of laboratory confirmed cases (104/111; 93.7%). To organize the response to the outbreak, a global team of WHO and other partners, including MSF and UNICEF, has been sent to Niger. Even though there are many challenges in battle against meningitis in Niger, immunization, antibiotics administration and strong disease surveillance are recommended techniques to cope with the current meningitis outbreak in Niger.

Meningococcal carriage in periods of high and low invasive meningococcal disease incidence in the UK: comparison of UKMenCar1-4 cross-sectional survey results.

BACKGROUND: The incidence of invasive meningococcal disease in the UK decreased by approximately four times from 1999 to 2014, with reductions in serogroup C and serogroup B disease. Lower serogroup C invasive meningococcal disease incidence was attributable to implementation of the meningococcal serogroup C conjugate vaccine in 1999, through direct and indirect protection, but no vaccine was implemented against serogroup B disease. UK Meningococcal Carriage surveys 1-3 (UKMenCar1-3), conducted in 1999, 2000, and 2001, were essential for understanding the impact of vaccination. To investigate the decline in invasive meningococcal disease incidence, we did a large oropharyngeal carriage survey in 2014-15, immediately before the changes to meningococcal vaccines in the UK national immunisation schedule. METHODS: UKMenCar4 was a cross-sectional survey in adolescents aged 15-19 years who were enrolled from schools and colleges geographically local to one of 11 UK sampling centres between Sept 1, 2014, and March 30, 2015. Participants provided an oropharyngeal swab sample and completed a questionnaire on risk factors for carriage, including social behaviours. Samples were cultured for putative Neisseria spp, which were characterised with serogrouping and whole-genome sequencing. Data from this study were compared with the results from the UKMenCar1-3 surveys (1999-2001). FINDINGS: From the 19 641 participants (11 332 female, 8242 male, 67 not stated) in UKMenCar4 with culturable swabs and completed risk-factor questionnaires, 1420 meningococci were isolated, with a carriage prevalence of 7·23% (95% CI 6·88-7·60). Carriage prevalence was substantially lower in UKMenCar4 than in the previous surveys: carriage prevalence was 16·6% (95% CI 15·89-17·22; 2306/13 901) in UKMenCar1 (1999), 17·6% (17·05-18·22; 2873/16 295) in UKMenCar2 (2000), and 18·7% (18·12-19·27; 3283/17 569) in UKMenCar3 (2001). Carriage prevalence was lower for all serogroups in UKMenCar4 than in UKMenCar1-3, except for serogroup Y, which was unchanged. The prevalence of carriage-promoting social behaviours decreased from 1999 to 2014-15, with individuals reporting regular cigarette smoking decreasing from 2932 (21·5%) of 13 650 to 2202 (11·2%) of 19 641, kissing in the past week from 6127 (44·8%) of 13 679 to 7320 (37·3%) of 19 641, and attendance at pubs and nightclubs in the past week from 8436 (62·1%) of 13 594 to 7662 (39·0%) of 19 641 (all p<0·0001). INTERPRETATION: We show that meningococcal carriage prevalence in adolescents sampled nationally during a low incidence period (2014-15) was less than half of that in an equivalent population during a high incidence period (1999-2001). Disease and carriage caused by serogroup C was well controlled by ongoing vaccination. The prevalence of behaviours associated with carriage declined, suggesting that public health policies aimed at influencing behaviour might have further reduced disease. FUNDING: Wellcome Trust, UK Department of Health, and National Institute for Health Research.

Neisseria meningitidis serogroup C causing primary polyarthritis in an octogenarian.

A man in his 80s presented to the hospital with a 36-hour history of fever, myalgia, bilateral shoulder and right knee pain. Joint fluid aspirates from his shoulders and right knee isolated Gram-negative diplococci. After failing to grow on standard and selective media, Neisseria meningitidis was identified by 16s PCR and subsequently typed as serogroup C. He had no clinical features of meningitis or meningococcaemia. Blood cultures were negative and an EDTA blood sample was negative for meningococcal ctrA gene. Urine PCR was negative for Neisseria gonorrhoeae He was treated successfully with two arthroscopic joint washouts of his right knee, aspirates of both shoulders, 40 days of intravenous ceftriaxone and intensive physiotherapy as both an inpatient and outpatient. In the literature, we have not found any previously documented cases of serogroup C meningococcus causing polyarticular primary septic arthritis in this age group or guidance on duration of antibiotic treatment. Literature on the impact of rehabilitation to baseline function was also found to be lacking. Although rare, primary meningococcal arthritis (PMA) should be considered as a differential diagnosis in cases of acute polyarticular septic arthritis. Polyarticular PMA in older adults may require prolonged rehabilitation before one might expect to return to premorbid function.

Analysis of a meningococcal meningitis outbreak in Niger - potential effectiveness of reactive prophylaxis.

BACKGROUND: Seasonal epidemics of bacterial meningitis in the African Meningitis Belt carry a high burden of disease and mortality. Reactive mass vaccination is used as a control measure during epidemics, but the time taken to gain immunity from the vaccine reduces the flexibility and effectiveness of these campaigns. Targeted reactive antibiotic prophylaxis could be used to supplement reactive mass vaccination and further reduce the incidence of meningitis, and the potential effectiveness and efficiency of these strategies should be explored. METHODS AND FINDINGS: Data from an outbreak of meningococcal meningitis in Niger, caused primarily by Neisseria meningitidis serogroup C, is used to estimate clustering of meningitis cases at the household and village level. In addition, reactive antibiotic prophylaxis and reactive vaccination strategies are simulated to estimate their potential effectiveness and efficiency, with a focus on the threshold and spatial unit used to declare an epidemic and initiate the intervention. There is village-level clustering of suspected meningitis cases after an epidemic has been declared in a health area. Risk of suspected meningitis among household contacts of a suspected meningitis case is no higher than among members of the same village. Village-wide antibiotic prophylaxis can target subsequent cases in villages: across of range of parameters pertaining to how the intervention is performed, up to 220/672 suspected cases during the season are potentially preventable. On the other hand, household prophylaxis targets very few cases. In general, the village-wide strategy is not very sensitive to the method used to declare an epidemic. Finally, village-wide antibiotic prophylaxis is potentially more efficient than mass vaccination of all individuals at the beginning of the season, and than the equivalent reactive vaccination strategy. CONCLUSIONS: Village-wide antibiotic prophylaxis should be considered and tested further as a response against outbreaks of meningococcal meningitis in the Meningitis Belt, as a supplement to reactive mass vaccination.

Carriage rates and risk factors during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11) in Tuscany, Italy: a cross-sectional study.

BACKGROUND: During 2015-2016 an outbreak of invasive meningococcal disease due to N. meningitidis serogroup C ST-11 (cc11) occurred in Tuscany, Italy. The outbreak affected mainly the age group 20-30 years, men who have sex with men, and the area located between the cities of Firenze, Prato and Empoli, with discos and gay-venues associated-clusters. A cross-sectional-survey was conducted to assess the prevalence and risk factors for meningococcal-carriage, in order to address public health interventions. METHODS: A convenience sample of people aged 11-45 years provided oropharyngeal swab specimens and completed questionnaires on risk factors for meningococcal carriage during a 3 months study-period, conducted either in the outbreak-area and in a control-area not affected by the outbreak (cities of Grosseto and Siena). Isolates were tested by culture plus polymerase chain reaction. Serogroup C meningococcal isolates were further characterized using multilocus sequence typing. Univariate and multivariate analyses were performed to estimate adjusted odds ratios (AORs) for meningococcal carriage. RESULTS: A total of 2285 oropharyngeal samples were collected. Overall, meningococcal carriage prevalence was 4.8% (n = 110), with nonencapsulated meningococci most prevalent (2.3%; n = 52). Among encapsulated meningococci, serogroup B was the most prevalent (1.8%; n = 41), followed by serogroup Y (0.5%; n = 11) and serogroup C (0.2%; n = 4); one carrier of serogroup E and one of serogroup Z, were also found (0.04%). Three individuals from the city of Empoli were found to carry the outbreak strain, C:ST-11 (cc11); this city also had the highest serogroup C carriage prevalence (0.5%). At the multivariate analyses, risk factors for meningococcal carriage were: illicit-drugs consumption (AOR 6.30; p < 0.01), active smoking (AOR 2.78; p = 0.01), disco/clubs/parties attendance (AOR 2.06; p = 0.04), being aged 20-30 years (AOR 3.08; p < 0.01), and have had same-sex intercourses (AOR 6.69; p < 0.01). CONCLUSIONS: A low prevalence of meningococcal serogroup C carriage in an area affected by an outbreak due to the hypervirulent N. meningitidis serogroup C ST-11 (cc11) strain was found. The city of Empoli had the highest attack-rate during the outbreak and also the highest meningococcal serogroup C carriage-prevalence due to the outbreak-strain. Multivariate analyses underlined a convergence of risk factors, which partially confirmed those observed among meningococcal outbreak-cases, and that should be considered in targeted immunization campaigns.

Doença meningocócica invasiva nas capitais da Região Sul do Brasil: características e tendências / Invasive meningococcal disease in the capitals of the Southern Region of Brazil characteristics and trends

Objetivos: Analisar a tendência, descrever mudanças no comportamento da doença meningocócica invasiva (DMI) e estimar o impacto da vacina conjugada do meningococo C (VCMC) nas capitais da região Sul do Brasil, no período de 1991 a 2015, assim como, investigar as características sociodemográficas, econômicas e de intervenções tecnológicas associadas aos casos pertencentes a cluster da doença no município de Curitiba (PR), no período de 2001 a 2014. Métodos: As áreas de estudo englobaram as capitais da Região Sul do Brasil: Curitiba (PR), Florianópolis (SC) e Porto Alegre (RS), a população de estudo abrangeu os casos de DMI notificados entre 1991 a 2015 à vigilância da doença e residentes nessas capitais. A definição de caso adotada foi a padronizada pelo Ministério da Saúde. As fontes de dados foram: vigilância da DMI, o Instituto Adolfo Lutz, o Instituto Brasileiro de Geografia e Estatística e o Instituto de Pesquisa e Planejamento Urbano de Curitiba. A tendência da incidência e mortalidade da DMI foi determinada pelo modelo de regressão polinomial. A intensidade e a direção da relação linear entre a taxa de incidência e os indicadores socioeconômicos, de saúde e sorogrupo foram analisadas pelo coeficiente de correlação de Pearson. O impacto da VCMC foi estimado pela Fração Prevenida na População, comparando as taxas de incidência de 2012 e 2015 com as de 2009. Investigou-se os potenciais fatores associados a casos pertencentes a cluster no período de 2001 a 2014 por meio das estimativas de odds ratio não ajustada e ajustadas pela regressão logística múltipla não condicional, com os respectivos intervalos de confiança de 95%. Resultados: No período de estudo, a DMI apresentou três comportamentos distintos nas capitais da região sul: i) epidêmico na década de 1990, ii) declínio das taxas na década de 2000, antes da introdução da VCMC na rotina de imunização e, iii) estacionário com taxas baixas entre 2011 e 2015, sob a influência da VCMC. Observamos nesses períodos a influência de fatores biológicos, socioeconômicos e de saúde na incidência dessas capitais. No estudo mais detalhado em Curitiba, apresentou-se associado aos casos pertencentes a cluster, ajustados no tempo e pela idade, residir em bairros de baixa renda (OR: 2,3, IC95%:1,1-4,5). O sorogrupo predominante foi o B com 65,4%, seguida pelo C com 24,5% e 8,3% pelo W. Possivelmente, em virtude da baixa incidência do sorogrupo C, não se verificou a redução na incidência total da DMI, nestas capitais. Entretanto, no período posterior a VCMC, os casos pelo sorogrupo C foram raros ou zerados na faixa etária destinada a vacinação em Curitiba e Florianópolis. Em Porto Alegre foram registrados casos pelo sorogrupo C na faixa etária vacinada e o sorogrupo W se destacou. Conclusão: A partir do início desse século houve declínio expressivo da incidência da DMI nas capitais da região Sul do país, antes mesmo da introdução da vacina, aproximando-se das taxas de DMI encontradas em países de elevada renda. Tais resultados são consistentes, com trabalhos que mostram uma associação da DMI com as condições de vida e grau de desenvolvimento das populações

Objectives: To analyze the trend and describe changes in the epidemiology of invasive meningococcal disease (IMD) and to estimate the impact of the meningococcal conjugate C vaccine (MCCV) in the capitals of the southern region of Brazil, from 1991 to 2015, as well as to investigate the sociodemographic, economic and technological interventions associated to the cases belonging in cluster of the disease in the city of Curitiba (PR), from 2001 to 2014. Methods: The study areas included the capitals of the States of Southern Brazil: Curitiba (PR), Florianópolis (SC) and Porto Alegre (RS), the study population considered cases of IMD reported between 1991 and 2015 to surveillance and residents in these capitals. The IMD case definition adopted was that standardized by the Ministry of Health. The data sources were the surveillance of the IMD, the Adolfo Lutz Institute, the Brazilian Institute of Geography and Statistics and the Institute of Research and Urban Planning of Curitiba. The trend of IMD incidence and mortality was determined by the polynomial regression model. The intensity and direction of the linear relationship between the incidence rate and socioeconomic indicators, health and serogroup were analyzed by the Pearson correlation coefficient. The impact of the MCCV was estimated by the Prevented Fraction for the Population comparing the incidence rates of 2012 and 2015 with those of 2009. We investigated the potential factors associated with cases belonging in cluster between 2001 and 2014 by the unadjusted and adjusted odds ratio estimates by the multiple unconditional logistic regression, with the respectives confidence intervals of 95%. Results: Between 1991 and 2015, IMD presented three distinct periods in the capitals of the southern region: i) epidemic in the 1990s, ii) decline in rates from 2000 to 2010, before the introduction of MCCV in immunization routine and (iii) stationary at low rates in 2011 to 2015, under the influence of MCCV. In this period, we observed the influence of biological, socioeconomic and health factors on the incidence of these capitals. In more detailed study in Curitiba, it was associated with cases belonging in cluster, adjusted in time and by age, to live in low-income neighborhoods (OR: 2.3, 95% CI: 1.1-4.5). Serogroup B was predominant with 65,4%, followed by C with 24,5% and 8,3% by W. Possibly, due to the low incidence of serogroup C, there was no reduction in the total incidence of IMD in these capitals. However, *in the period after MCCV, serogroup C cases were rare or zero in the age group destinedfor vaccination in Curitiba and Florianópolis. In Porto Alegre, cases were registered by serogroup C in the vaccinated age group and serogroup W was relevant. Conclusion: From the beginning of this century there was a significant decline in the incidence of IMD in the capitals of the southern region of the country, even before the introduction of the vaccine, approaching IMD rates found in high income countries. These results are consistent, with studies showing an association of IMD with living conditions and the degree of population development

Seroprevalence of bactericidal antibodies against serogroup B and C Meningococci in a University Hospital

Meningococcus serogroup B (MenB), clonal complex 32 (cc 32), was the Brazilian epidemic strain of meningococcal disease (MD) in the 1990’s. Currently, meningococcus serogroup C (MenC), cc 103, is responsible for most of the cases of the disease in Brazil. The aim of this study was to investigate the seroprevalence of bactericidal antibody (SBA) against representative epidemic strains of MenC, (N753/00 strain, C:23:P1.22,14-6, cc103) and MenB, (Cu385/83 strain, B:4,7:P1.15,19, cc32) in students and employees of a university hospital in the State of Rio Grande do Sul (RS, Brazil). A second MenC strain (N79/96, C:2b:P1.5-2,10, cc 8) was used as a prototype strain of Rio de Janeiro’s outbreak that occurred in the 1990’s. Our previous study showed a 9% rate of asymptomatic carriers in these same individuals. A second goal was to compare the SBA prevalence in meningococcal carriers and non-carriers. Fifty-nine percent of the studied population showed protective levels of SBA titers (log2≥2) against at least one of the three strains. About 40% of the individuals had protective levels of SBA against N753/00 and Cu385/83 strains. Nonetheless, only 22% of the individuals showed protective levels against N79/96 strain. Significantly higher antibody levels were seen in carriers compared to non-carriers (P≤0.009). This study showed that, similar to other States in Brazil, a MenC (23:P1.22,14-6, cc103) strain with epidemic potential is circulating in this hospital. Close control by the Epidemiological Surveillance Agency of RS of the number of cases of MD caused by MenC strains in the State is recommended to prevent a new disease outbreak.

Impacto da implantação da vacina conjugada na incidência de meningite meningocócica do tipo C em crianças menores de cinco anos no Sul de Santa Catarina / Impact of the conjugated vaccine implementation on the incidence of meningococcal meningitis type C in children under five in southern Santa Catarina

Introdução: A Doença Meningocócica (DM) é uma infecção bacteriana aguda causada pela Neisseria meningitidis. Acomete principalmente crianças menores de cinco anos, sobretudo as menores de um ano. Suas manifestações clínicas variam desde doença leve até síndrome séptica e/ou meningite. Diante da letalidade da doença, o Ministério da Saúde incluiu no calendário vacinal, no segundo semestre de 2010, a vacina adsorvida meningocócica C (conjugada). Justificativa: Considerando a recente implementação da vacina no serviço público, é necessário avaliar o impacto desta na saúde da população. Este estudo tem como objetivo descrever a ocorrência de Meningite Meningocócica do tipo C em crianças menores de cinco anos na macrorregional Sul do Estado de Santa Catarina dois anos antes (2008 e 2009) e dois anos depois (2011-2012) após a campanha vacinal contra o meningococo C, realizada no ano de 2010. Métodos: Este é um estudo observacional do tipo transversal. Resultados/Discussão: No período estudado, houve apenas cinco casos confirmados de doença meningocócica. O baixo número de casos deve-se provavelmente à ampla utilização da vacina em clínicas particulares já em anos anteriores aos estudados. Nenhuma criança morreu devido à meningite meningocócica ou meningococcemia, sendo que estudos no Brasil em períodos anteriores à vacinação mostraram letalidade em torno de 20%. Conclusão: O menor número de casos e menor mortalidade pela DM demonstram maior efetividade da Vigilância Epidemiológica e efetividade do diagnóstico precoce (AU)

Introduction: Meningococcal disease (MD) is an acute bacterial infection caused by Neisseria meningitidis. It mainly affects children under five years of age, especially children under one year. Its clinical manifestations range from mild disease to septic syndrome and/or meningitis. Given the lethality of the disease, the Ministry of Health included the adsorbed meningococcal C vaccine (conjugated) in the vaccine calendar in the second half of 2010. Justification: Considering the recent implementation of the vaccine in the public service, it is necessary to evaluate its impact on the health of the population. This study aims to describe the occurrence of Meningococcal Meningitis type C in children under five years of age in the southern macro-region of the State of Santa Catarina two years before (2008-2009) and two years after (2011-2012) the vaccination campaign against meningococcus C carried out in 2010. Methods: This is an observational cross-sectional study. Results/Discussion: In the study period, there were only five confirmed cases of meningococcal disease. The low number of cases is likely due to the wide use of the vaccine in private clinics already years before those studied here. No child died due to meningococcal meningitis, and studies in Brazil prior to vaccination show lethality around 20%. Conclusion: The lower number of cases and lower mortality due to MD demonstrate greater effectiveness of the Epidemiological Surveillance and the effectiveness of early diagnosis (AU)

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage.

The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.

[Meningococcal vaccines in France] / Vaccination antiméningococcique en France

Meningococcal vaccines in france. In France in 2015, several vaccines against invasive meningococcal disease (IMD) are available: non-conjugated polysaccharide vaccines (bivalent AC and tetravalent ACYW135) conjugate vaccines (monovalent A monovalent C and quadrivalent ACYW135) and a novel multicomponent meningococcal B vaccine. These vaccines have a very satisfactory safety profile. Currently in France, universal vaccination against serogroup C meningococcal disease is recommended for all infants at the age of 12 months with catch up till the age of 24 years. Vaccination against IMD B and C are also recommended to persons with specific individual risk factors (mainly asplenia, complement deficiency, hematopoietic stem cells) or travel in endemic areas. Despite recommendations, vaccination coverage remains below recommended levels in most of the targeted populations.

Vaccination antiméningococcique en france. En France en 2015, plusieurs vaccins contre les infections invasives à méningocoques (IIM) sont disponibles : des vaccins polyosidiques non conjugués (bivalent AC et tétravalent ACYW135), des vaccins conjugués (monovalent C et tétravalent ACYW135) et le vaccin protéique contre le méningocoques de sérogroupe B. Tous ces vaccins ont un profil de tolérance très satisfaisant. À l'heure actuelle, en France, une vaccination universelle contre les infections à méningocoque de sérogroupe C est recommandée pour tous les nourrissons à 12 mois avec rattrapage jusqu'à l'âge de 24 ans. Il existe également des recommandations de vaccination contre les infections à méningocoques C et B en fonction de facteurs de risque particuliers (principalement asplénie, déficit en complément, greffe de cellules souches hématopoïétiques) ou de voyage en zone d'endémie. Malgré ces recommandations, la couverture vaccinale reste cependant inférieure aux préconisations dans la plupart des populations ciblées.

Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells.

The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.

Diagnostic value of polymerase chain reaction analysis of skin biopsies in purpura fulminans.

Even though prompt diagnosis and treatment of purpura fulminans (PF) is essential to reduce mortality, early administration of antibiotics may preclude identification of the causative agent by standard bacterial cultures and thus render definitive diagnosis impossible. Here we present a case of an infant with PF and negative bacterial cultures for whom polymerase chain reaction (PCR) analysis of a cutaneous biopsy specimen obtained 4 days after initiation of antibiotics identified the genomic sequence of Neisseria meningitidis genogroup C. When bacterial cultures fail to provide useful information, PCR of skin biopsy specimens can be a valuable diagnostic tool in PF.

Impacto da vacinação contra o meningococo c na ocorrência de doença meningocócica em hospital especializado / The impact of vaccination against meningococcus c on the occurrence of meningococcal disease in a specialized hospital / El impacto de la vacunación contra el meningococo c en la ocurrencia de la enfermedad meningocócica en un hospital especializado

A Doença Meningocócica (DM) constitui-se um grave problema de saúdepública devido a sua alta letalidade. O objetivo deste estudo é descrever a ocorrência da DM em um serviço de referência cinco anos antes (2005 a 2009) e um ano e oito meses (2011 a agosto 2012) após a campanha vacinal em Salvador, observando possíveis alterações no perfil epidemiológico. Trata-se de um estudo descritivo, utilizando dados secundários coletados no Núcleo de Vigilância Epidemiológica do Hospital Couto Maia, com análise retrospectiva dos casos de DM no período estudado. A amostra foi formada por 488 pacientes, tendo sido amaior parte deles internados no período pré-vacinal (71por cento). Os resultados apontam uma queda na frequência importante da doença nas faixas etárias de 0 a 5 anos e entre 20 e 24 anos, 90por cento e 85por cento, respectivamente. O estudo obteve resultados compatíveis com estudos prévios realizados no Reino Unido e em Quebec, evidenciando diminuição da frequência deDM nas faixas etárias vacinadas contra o meningococo C. Concluiu-se que a vacinação contra o meningococo C, mesmo sendo restrita a algumas faixas etárias, pode constituir importante ferramenta para redução dos casos da doença.

The Meningococcal Disease (DM) constitutes a serious public health problem due to its high lethality. The aim of this study is to describe the occurrence of DM in a reference service five years before (2005-2009) and one year and eight months (2011 to August 2012) after the vaccination campaign in Salvador, observing possible changes in the epidemiological profile. This is a descriptive study using secondary data collected at the Center for Epidemiological Surveillance of Hospital Couto Maia, with retrospective analysis of cases of DM during the study period. The sample consisted of 488 patients, who were mostly admitted tothe pre-vaccine period (71percent). The results indicate a significant decrease in the frequency of the disease in the age groups 0-5 years and between 20 and 24 years, 90percent and 85percent, respectively. The study obtained results consistent with previous studies conducted in the UK and in Quebec,showing a reduction in the frequency of DM in the age vaccinated against meningococcal C. It was concluded that vaccination against meningococcal C, despite being restricted to certain age groups can be an important tool for reducing cases of meningococcal disease.

La enfermedad meningocócica (EM) constituye un grave problema de salud pública debido a su alta letalidad. El objetivo de este estudio es describir la ocurrencia de EM en un servicio de referencia, durante el periodo de 2005 a 2009, y en un periodo más reciente, de 2011 a agosto de 2012, después de la campaña de vacunación en Salvador, observando los posibles cambios en el perfil epidemiológico. Se trata de un estudio descriptivo utilizando datos secundarios recolectados en el Centro de Vigilancia Epidemiológica del Hospital Couto Maia, con el análisis retrospectivo de los casos de DM durante el período de estudio. La muestra estuvo constituida por 488 pacientes, en su mayoría (71por ciento), ingresados en el periodo anterior a la vacuna. Los resultados indican una disminución significativa en la frecuencia de la enfermedad en los grupos de edad 0-5 años y entre 20 y 24 años, es decir, 90por ciento y 85por ciento, respectivamente. Los resultados obtenidos son compatibles con estudios previos realizados en el Reino Unido y en Quebec, mostrando unareducción de la frecuencia de EM en los grupos de edad vacunados contra el meningococo C. Se concluye que la vacunación contra el meningococo C, a pesar de su restricción a ciertos grupos de edad, puede ser una herramienta importante para reducir los casos de dichaenfermedad

[Immunisation schedule of the Spanish Association of Paediatrics: 2013 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2013.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded as routine vaccinations those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunisation schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, CAV-AEP follows the innovations proposed in the last year's schedule, such as the administration of the first dose of the MMR and the varicella vaccines at age 12 months and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age, preferably at 11-12 years. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years, preferably at 11-12 years, must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it emphasizes the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule.

Aspectos epidemiológicos da doença meningocócica no Distrito Federal, 2000 a 2011 / Epidemiological aspects of meningococcal disease in the Distrito Federal from 2000 to 2011

Objetivos: Analisar o comportamento da doença meningocócica (DM) no Distrito Federal (DF), no período de 2000 a 2011, investigar fatores associados à gravidade da doença e avaliar o impacto da introdução, em 2010, da vacina conjugada contra o meningococo C. Métodos: Trata-se de um estudo com um componente descritivo e outro analítico, abrangendo os residentes no DF que apresentaram DM. Foram incluídos os casos confirmados de DM registrados nos sistemas de informação de notificação e/ou de mortalidade e/ou do laboratório. Para a investigação de fatores associados ao óbito por DM, a variável dependente foi evolução e as variáveis independentes foram sexo, idade, forma clínica e sorogrupo da Neisseria meningitidis. Na avaliação do impacto da introdução da vacina conjugada contra o meningococo C, foram comparadas as taxas de incidência do período pré e pósvacina, por grupo etário. Resultados: Foram analisados 490 casos confirmados de DM no período. A cepa que predominou antes de 2005 foi a B:4,7:P1.19,15 com 67,8 por cento (61/90) e, a partir desse ano, predominaram as cepas C:23:P1.14-6 com 40,9 por cento (61/149) e C:2a:P1.5,2 com 12,8 por cento (19/149). As taxas médias anuais de incidência e de mortalidade por DM, no período, foram, respectivamente, 1,7 e 0,4/100.000 habitantes/ano e a letalidade média foi 21 por cento . A taxa de incidência de DM foi maior nas crianças menores de um ano, variando de 13,1 em 2011 a 38,7/100.000 habitantes/ano em 2000. A letalidade foi maior no grupo de 40 anos e mais, 40 por cento , e entre as crianças com dois anos, 32 por cento . A região administrativa (RA) do Paranoá foi a que apresentou as mais elevadas taxas médias anuais de incidência, 3,3/100.000 habitantes, e de mortalidade, 0,6/100.000 habitantes. Os menores de dois anos e os com idade maior ou igual a 30 anos tiveram risco significativamente maior para óbito, assim como as formas clínicas meningococcemia e meningite com meningococcemia. Houve uma redução estatisticamente significativa (p = 0,02) da incidência de DM em menores de dois anos do ano de 2009, 21,3/100.000 habitantes/ano, para o ano de 2011, 6,6/100.000 habitantes/ano. Conclusão: Esse estudo possibilitou verificar os grupos etários mais atingidos por DM, os fenótipos circulantes, as RA com as maiores taxas de incidência e de mortalidade e fazer uma avaliação preliminar do impacto da vacina conjugada contra o sorogrupo C, após o primeiro ano de sua introdução no calendário infantil de imunização.

B cell memory to a serogroup C meningococcal conjugate vaccine in childhood and response to booster: little association with serum IgG antibody.

The maintenance of adequate serum Ab levels following immunization has been identified as the most important mechanism for individual long-term protection against rapidly invading encapsulated bacteria. The mechanisms for maintaining adequate serum Ab levels and the relationship between Ag-specific memory B cells and Ab at steady state are poorly understood. We measured the frequency of circulating serogroup C meningococcal (MenC)-specific memory B cells in 250 healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming, before a booster of a combined Haemophilus influenzae type b-MenC conjugate vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the relationship between circulating MenC-specific memory B cell frequencies and Ab at baseline and following the booster vaccine. We found very low frequencies of circulating MenC-specific memory B cells at steady state in primary school-aged children and little association with MenC IgG Ab levels. Following vaccination, there were robust memory B cell booster responses that, unlike Ab levels, were not dependent on age at priming with MenC. Measurement of B cell memory in peripheral blood does not predict steady state Ab levels nor the capacity to respond to a booster dose of MenC Ag.

Análise crítica das recomendações do uso das vacinas meningocócicas conjugadas / A critical appraisal of the recommendations for the use of meningococcal conjugate vaccines

OBJETIVOS: Analisar a epidemiologia da doença meningocócica no Brasil e o impacto que as recentes evidências acumuladas com a incorporação das vacinas meningocócicas C conjugadas nos programas de imunização podem ter nas diferentes estratégias de uso dessas vacinas. FONTES DOS DADOS: Revisão nas bases de dados MEDLINE, SciELO e LILACS no período de 2000 a 2011. SÍNTESE DOS DADOS: No Brasil, a doença meningocócica é endêmica, com ocorrência periódica de surtos. Os maiores coeficientes de incidência ocorrem em lactentes, sendo o sorogrupo C responsável pela maioria dos casos, motivando a introdução da vacina meningocócica C conjugada no Programa Nacional de Imunizações, em 2010, para crianças menores de 2 anos. A introdução das vacinas meningocócicas C conjugadas nos programas de imunização na Europa, Canadá e Austrália mostrou-se efetiva, com dramática redução na incidência de doença causada pelo sorogrupo C, não apenas nos vacinados, mas também em não vacinados. A efetividade em longo prazo dessas vacinas mostrou-se dependente de uma combinação de persistência de anticorpos, memória imunológica e proteção indireta. Recentes evidências indicando que a persistência de anticorpos não é duradoura em crianças pequenas imunizadas e que a memória imunológica não é rápida o suficiente para protegê-las contra a doença enfatizam a importância da proteção indireta para manutenção da população protegida. CONCLUSÕES: A rápida queda de títulos de anticorpos em crianças vacinadas nos primeiros anos de vida sugere a necessidade de incorporarmos doses de reforço antes da adolescência, especialmente em locais como o Brasil, onde ainda não contamos com o efeito da proteção indireta da população.

OBJECTIVES: To assess the epidemiology of meningococcal disease (MD) in Brazil and the impact that recent evidence and lessons learned from the introduction of meningococcal C conjugate (MCC) vaccines into immunization programs may have on different strategies of vaccine use. SOURCES: Non-systematic review of the MEDLINE, SciELO and LILACS databases covering the period from 2000 to 2011. SUMMARY OF THE FINDINGS: Meningococcal disease is endemic in Brazil, with periodic occurrence of outbreaks. Most cases are associated with serogroup C and the highest incidence rates are observed in infants, encouraging the introduction of MCC vaccine in the National Immunization Program in 2010 for children under 2 years old. The introduction of MCC vaccines into immunization programs in Europe, Canada and Australia proved to be effective, with dramatic reduction in the incidence of serogroup C meningococcal disease, not only in the vaccinated, but also in the unvaccinated individuals. Long-term effectiveness of MCC vaccines was dependent on a combination of antibody persistence, immunologic memory and herd protection. Recent evidence indicating that antibody persistence is not long-lasting in young immunized children, and that immunologic memory is not fast enough to protect them against the disease, emphasize the importance of herd protection to maintain the population protected. CONCLUSIONS: The rapid decline of antibody titers in children vaccinated in the first years of life suggests the need to incorporate booster doses before adolescence, especially in locations like Brazil, where the immunization program did not incorporate catch-up campaigns including adolescents, lacking the herd immunity effect.

Meningococcal group C and w135 immunological hyporesponsiveness in african toddlers.

A phase II clinical study was conducted in African toddlers (aged 12 to 23 months), with subjects receiving either investigational meningococcal group A conjugate (PsA-TT), meningococcal ACWY polysaccharide (PsACWY), or Haemophilus influenzae type b (Hib-TT) vaccine. Ten months following vaccination, the 3 study groups were further randomized to receive a dose of PsA-TT, a 1/5 dose of PsACWY, or a dose of Hib-TT vaccine. Group A serum bactericidal antibody (SBA) results have been reported previously, with PsA-TT demonstrating superior immunogenicity versus PsACWY vaccine. Immunogenicity for serogroups W135 and C was assessed by SBA assay to investigate the impact of multiple doses in this age group. Blood samples were taken prior to vaccination, 28 days and 40 weeks post-primary vaccination, and 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY. Subjects who had previously received a full dose of PsACWY had W135 SBA geometric mean titers (GMTs) of 26.1 and 4.4 at 7 and 28 days post-booster vaccination with a 1/5 PsACWY dose, respectively, whereas the W135 SBA GMTs of naïve subjects at these time points following vaccination with a 1/5 dose of PsACWY were 861.1 and 14.6, respectively. Similar differences were observed for serogroup C, with SBA GMTs of 99 and 5.9 at 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY, respectively, for naïve subjects, compared to 4.1 and 3.2 for previously vaccinated subjects. Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naïve subjects receiving a 1/5 dose of PsACWY vaccine.

Fatal meningococcal meningitis in a HIV-infected patient caused by serogroup C Neisseria meningitidis belonging to the non-hypervirulent clonal complex ST-60 (cc60)

Meningococcal strains belonging to clonal complex cc60 are not associated with hypervirulent lineages and were never reported as causing disease in Latin American countries. This is the first report of a fatal meningitis case caused by a cc60 clonal complex meningococcus in Brazil. Despite the immune-compromised state of the patient, the fatal outcome here described shows the potential pathogenic behavior of strains belonging to this clonal complex and how compromised hosts can be susceptible to meningococcal infections even if the strain is not particularly invasive.

Suppressive effect of bacterial polysaccharides on BAFF system is responsible for their poor immunogenicity.

Capsular polysaccharides of encapsulated bacteria are weakly immunogenic T cell-independent type 2 (TI-2) Ags. Recent findings suggest that BAFF system molecules have a critical role in the development of Ab responses against TI-2 Ags. In this study, we investigated the effect of bacterial polysaccharides on B cell responses to BAFF and a proliferation-inducing ligand (APRIL). We determined that B cells exposed to meningococcal type C polysaccharide (MCPS) or group B Streptococcus serotype V (GBS-V) were unresponsive to BAFF- and APRIL-induced Ig secretion. Moreover, MCPS and GBS-V strongly downregulated transmembrane activator and calcium-modulator and cyclophilin ligand interactor, the BAFF and APRIL receptor that is responsible for Ab development against TI-2 Ags. Interestingly, (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll), a prototype TI-2 Ag, did not manifest a suppressive effect on B cells. Paradoxically, whereas GBS-V and MCPS inhibited IFN-γ-induced BAFF production from dendritic cells, NP-Ficoll strongly increased BAFF secretion. TLR 9 agonist CpG deoxyoligonucleotide (ODN) was able to reverse the MCPS-mediated transmembrane activator and calcium-modulator and cyclophilin ligand interactor suppression but could not rescue the Ig secretion in BAFF- or APRIL-stimulated B cells. In support of these in vitro observations, it was observed that CpG ODN could help augment the Ab response against NP in mice immunized with a CpG ODN-containing NP-Ficoll vaccine but exhibited only marginal adjuvant activity for MCPS vaccine. Collectively, these results suggest a mechanism for the weak immunogenicity of bacterial polysaccharides and explain the previously observed differences between bacterial polysaccharide and NP-Ficoll immunogenicity.