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)

Control of meningitis in Sudan

Following the deployment implementation of mass preventive campaign with Conjugate-A vaccines [MenAfriVac] in Sudan in 2013, cases of meningococcal meningitis caused by Neisseria Meningitidis serogroup A [NmA] has decreased substantially in the country. However, concerns remains on the possibility of outbreaks caused by new sero-group particularly serogroup C

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

Evaluation of safety of meningococcal group AC bivalent polysaccharide conjugate vaccine in children aged 5-24 months old / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the safety of meningococcal group AC bivalent polysaccharide conjugate vaccine among children aged 5-24 months old.</p><p><b>METHODS</b>From July 2011 to June 2012, a total of 34 411 children aged 5-24 month-old who voluntarily vaccinated meningococcal group AC bivalent polysaccharide conjugate vaccine in Zhongshan city were included. The adverse effects within 72 hours were recorded and analyzed.</p><p><b>RESULTS</b>34 411 children were recruited, including 18 708 boys (54.36%), whose mean age were ( 11.4 ± 3.9 ) months old.Within 72 hours, the incidence rates of local adverse effects were 0.76% (261/34 411) for erythema,0.57% (197/34 411) for sclerosis,0.56% (191/34 411) for swelling,0.42% (143/34 411) for pain,0.15% (53/34 411) for pruritus, and 0.15% (50/34 411) for rash on the injection site. The overall incidence rate of local adverse effects was 1.61% (554/34 411; 95%CI:1.48%-1.74%). The incidence rates of systemic adverse effects were 0.98% (312/34 411) for fever,0.48% (164/34 411) for anorexia,0.31% (108/34 411) for diarrhea,0.29% (100/34 411) for malaise,0.20% (70/34 411) for nausea and vomiting, and 0.08% (26/34 411) for headache. The overall incidence rate of systemic adverse effects was 1.64% (565/34 411; 95%CI:1.51%-1.78%).25 children (0.07%) had hyperpyrexia ( > 39°C), and the time of duration lasted less than 48 hours.16 children (0.05%) had symptoms of cold, such as cough and catarrh.No accident and other serious events were reported. The incidence rate of systemic adverse effects among boys was 1.79% (334/18 708), which was higher than that of girls (1.47%, 231/15 703), the difference showed statistical significance (χ(2) = 5.22, P < 0.01). The incidence rate of systemic adverse effects among children aged 5-12 month-old was 1.78% (411/23 113), which was higher than that among children aged 13-24 month-old (1.36%, 154/11 298), the difference showed statistical significance (χ(2) = 8.10, P < 0.01). The incidence rate of local adverse effects in children vaccinated the first dose was 1.72% (536/31 129), which was higher than that in children vaccinated the second or third dose (0.55%, 18/3282), the difference showed statistical significance (χ(2) = 25.81, P < 0.01). The incidence rate of systemic adverse effects in children vaccinated the first dose was 1.73% (539/31 129), which was higher than that in children vaccinated the second or third dose (0.79%, 26/5282), whose difference also showed statistical significance (χ(2) = 16.22, P < 0.01).</p><p><b>CONCLUSION</b>The safety of meningococcal group AC bivalent polysaccharide conjugate vaccine among children aged 5-24 months old is relative good.</p>

Patterns of meningococcal infection in Sudan with emergence of Neisseria meningitidis serogroup W135

This study was conducted during the 2004-2006 epidemic of meningitis in Sudan to follow-up the frequency of disease outbreak or endemic waves and to evaluate the new quadrivalent vaccine for actual application. Samples were collected from Darfur, El Gedaref, Kassala and Khartoum States and transported to the National Health Central Laboratory in Khartoum. Of 196 patients with clinical symptoms and signs of meningitis, conventional culture identified Neisseria meningitidis in 37 [18.9%], confirmed by polymerase chain reaction. N. meningitidis type A was identified in 29 [78.4%] patients, type C in 3 [8.1%] and N. meningitidis W135 in 5 [15.5%]. The serotyping and molecular diagnosis patterns of N. meningitidis showed the emergence of the new strain,W 135, in patients from the borders of Sudan, 3 from the West Darfur, and 1 each from El Gedaref and Kassala. These could be related to the movement of pilgrims through the borders to Saudi Arabia in the Hajj season. Serious consideration may be needed for quadrivalent vaccination to prevent seasonal and Hajj season outbreaks

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.

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.

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.

Proteome analysis of Neisseria meningitidis serogroup strains C associated with outbreaks in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>During 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed.</p><p><b>METHODS</b>Clinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry.</p><p><b>RESULTS</b>502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426.</p><p><b>CONCLUSIONS</b>The different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.</p>

[Pleural effusion with pneumonia caused by Neisseria meningitidis C: a case report]

Pleural effusion with pneumonia is an uncommon manifestation of Neisseria meningitidis infection. We report the case of a 3-year-old child who presented a one week fever and abdominal pain. Chest X ray showed pleural effusion with lung condensation. The outcome was favourable with antibiotics

Neonatal sepsis and meningitis caused by Neisseria meningitidis: a case report

OBJECTIVE: To report a full-term newborn infant that developed a sepsis associated to meningitis caused by Neisseria meningitidis serogroup C on the 14th day of life. CASE DESCRIPTION: The patient was a term female infant, born to a mother with Systemic Lupus Erythematosus, with birth weight of 2,610g, Apgar Score 1, 4 and 8, who needed mechanical ventilation for 24 hours. On the 7th day of life, the neonate was discharged from the hospital with good overall condition. On the 15th day of life, the newborn infant presented fever and respiratory failure. The cerebrospinal fluid showed 1042 cells/mm³, with neutrophilic predominance, protein of 435 mg/dL, and glucose < 10 mg/dL. The blood and the cerebrospinal fluid cultures were positive for Neisseria meningitidis serogroup C. The neonate was hospitalized, needing mechanical ventilation and vasoactive drugs, and received 21 days of crystalline penicillin. After hospital discharge, there were no signs of neurological sequels and the infant was able to be breastfed. The case report presents a unique situation: an uncommon etiology of neonatal meningitis and favorable evolution, despite neurological sequels reported in the literature. This report emphasizes the need to prevent the premature exposure of newborn infants to pathological agents, especially if they presented birth injuries and/or are preterm, due to their lack of immunological capacity.

OBJETIVO: Relatar o caso de um recém-nascido de termo que apresentou no 14° dia de vida sepse associada à meningite, cujo agente etiológico foi a Neisseria meningitidis sorotipo C. DESCRIÇÃO DO CASO: recém-nascido de termo, cuja mãe é portadora de lupus eritematoso sistêmico, feminino, peso de nascimento de 2610g, Escala de Apgar 1, 4 e 8, sendo intubado e ventilado por 24 horas. Recebeu alta no 7° dia de vida em boas condições. No 15° dia de vida apresentou febre e desconforto respiratório. O líquido cefalorraquidiano mostrou 1042 células/mm³, com predomínio de neutrófilos, proteinorraquia de 435 mg/dL e glicorraquia < 10 mg/dL; a bacterioscopia revelou a presença de diplococos. Foi internado na Terapia Intensiva Neonatal, necessitou de ventilação mecânica e de drogas vasoativas. A hemocultura e a cultura do líquido cefalorraquidiano foram positivas para Neisseria meningitidis C. O recém-nascido foi tratado por 21 dias com penicilina cristalina. Recebeu alta hospitalar em boas condições, em aleitamento materno exclusivo e sem seqüelas neurológicas. O caso descrito apresenta como peculiaridades: etiologia incomum de meningite neonatal e evolução favorável, apesar dos relatos em literatura mostrarem seqüelas neurológicas. Destaca-se ainda, a necessidade de enfatizar a não exposição precoce do recém-nascido, especialmente se tiver tido agravos ao nascimento ou for prematuro, devido à sua inexperiência imunológica.

Molecular typing of Neisseria meningitidis serogroup C strains with pulsed field gel electrophoresis in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the characteristics of epidemiology and molecular typing on Neisseria meningitidis serogroup C strains associated with outbreaks of Anhui province and sporadic cases in China, using pulsed field gel electrophoresis (PFGE).</p><p><b>METHODS</b>212 Neisseria meningitidis serogroup C strains were isolated from invasive meningococcal cases, close contacts and healthy carriers, including 48 strains from Anhui province with 38 strains associated with serogroup C outbreaks. PFGE were performed by genomic DNA digestion with Nhe I restriction enzyme. The results of PFGE were analyzed by BioNumerics software (Version 4.0, Applied Maths BVBA, Belgium).</p><p><b>RESULTS</b>A total number of 212 Neisseria meningitidis serogroup C isolates were typed by 43 patterns, named AH1 to AH43. In China, AH1 pattern was the major PFGE pattern with 69.3% (n = 147) of all strains, distributed in 11 provinces. Three types of PFGE patterns (AH1 to AH3) were found in 48 strains from Anhui province, in which, 93.8% (n = 45) belonged to AH1. 97.4% (n = 37) of 38 strains associated with serogroup C outbreaks in Anhui province showed AH1 pattern. A total of 53 serogroup C strains were isolated from invasive meningococcal cases with 67.9% (36/53) of AH pattern. 71.9% (87/121) of serogroup C strains isolated from contacts of invasive meningococcal cases was AH1 pattern and 63.2% (24/38) of the strains from healthy carriers showed AH1 pattern.</p><p><b>CONCLUSION</b>By PFGE typing and analysis, AH1 pattern of Neisseria meningitidis serogroup C strains was proved to be the main clone which causing the outbreaks in Anhui province and might be responsible for the sporadic serogroup C meningococcal disease epidemics else where in the country.</p>

Neisseria meningitidis serogroup C polysaccharide production by varying the bacteria inoculum and the initial glucose concentration

A produção de polissacarídeo para a produção de vacina específica contra N. meningitidis sorogrupo C é o principal produto obtido dos cultivos deste microorganismo. Para uma análise comparativa da produção de polissacarídeo variando as quantidades de inóculo e as concentrações iniciais de glicose, realizaram-se quatro ensaios, empregando planejamento fatorial 22, em duplicata. As amostras foram retiradas a cada duas horas para a determinação da concentração celular, pH, glicose e concentração de polissacarídeo. O critério analítico foi baseado na concentração final de polissacarídeo e no fator de conversão célula/polissacarídeo (YP/X). Os melhores resultados de concentração final de polissacarídeo (0,105 g/L) e YP/X(0,078) ocorreram na condição de cultivo com maior inóculo (densidade óptica de cerca de 0,1 a 540 nm). O polissacarídeo obtido ao final desse cultivo foi eluído em gel-cromatografia para determinação de peso molecular, sendo um antígeno adequado para a produção da vacina.

Controle de surto de meningite meningocócica do sorogrupo C no Município de Corupá, Santa Catarina, Brasil, com ações rápidas e efetivas de vigilância epidemiológica e imunização / Control of a community outbreak of group C meningococcal meningitis in Corupá, Santa Catarina State, Brazil, based on rapid and effective epidemiological surveillance and immunization

No ano de 2001, num período de sete dias, em município de pequeno porte localizado na região norte de Santa Catarina, Brasil, foram registrados oito casos de doença meningocócica entre adolescentes e adultos jovens, correspondendo a uma taxa de ataque de 367,5 casos/100 mil habitantes deste segmento populacional. Exames laboratoriais identificaram o meningococo do sorogrupo C em três dos oito casos, o que permitiu utilizar, de acordo com os critérios estabelecidos pelo Ministério da Saúde do Brasil, a estratégia do bloqueio vacinal anti-C para o controle do agravo naquela população sob risco. A vacinação foi levada a todas as pessoas maiores de dois anos de idade, residentes no município. A ausência de casos da doença meningocócica naquela comunidade nos 12 meses após o bloqueio vacinal sinaliza para a importância da pronta intervenção no controle de surtos pela enfermidade.

Polysaccharide production in batch process of Neisseria meningitidis serogroup C comparing Frantz, modified Frantz and Cartlin 6 cultivation media

Polysaccharide of N. meningitidis serogroup C constitutes the antigen for the vaccine against meningitis. The goal of this work was to compare three cultivation media for production of this polysaccharide: Frantz, modified Frantz medium (with replacement of glucose by glycerol), and Catlin 6 (a synthetic medium with glucose). The comparative criteria were based on the final polysaccharide concentrations and the yield coefficient cell/polysaccharide (Y P/X). The kinetic parameters: pH, substrate consumption and cell growth were also determined. For this purpose, 9 cultivation runs were carried out in a 80 L New Brunswick bioreactor, under the following conditions: 42 L of culture medium, temperature 35°C, air flow 5 L/min, agitation frequency 120 rpm and vessel pressure 6 psi, without dissolved oxygen or pH controls. The cultivation runs were divided in three groups, with 3 repetitions each. The cultivation using the Frantz medium presented the best results: average of final polysaccharide concentration = 0.134 g/L and Y P/X=0.121, followed by Catlin 6 medium, with results of 0.095 g/L and 0.067 respectively. Considering the principal advantages in the use of the synthetic medium, i.e. facilitation of a cultivation and purification steps of the polysaccharide production process, there is a possibility that in the near future, Catlin 6 will replace the traditional Frantz medium.

Critical analysis of old and new vaccines against N. meningitidis serogroup C, considering the meningococcal disease epidemiology in Brazil

Worldwide, the impact of meningococcal disease is substantial, and the potential for the introduction and spread of more virulent strains of N. meningitidis or strains with increased resistance to current antibiotics causes concern, making prevention essential. OBJECTIVES: Review the indications for meningococcal disease vaccines, considering the epidemiological status in Brazil. METHODS: A critical literature review on this issue using the Medline and Lilacs databases. RESULTS: In Brazil, MenB and MenC were the most important serogroups identified in the 1990s. Polysaccharide vaccines available against those serogroups can offer only limited protection for infants, the group at highest risk for meningococcal disease. Additionally, polysaccharide vaccines may induce a hypo-responsive state to MenC. New meningococcal C conjugate vaccines could partially solve these problems, but it is unlikely that in the next few years a vaccine against MenB that can promote good protection against multiple strains of MenB responsible for endemic and epidemic diseases will become available. CONCLUSIONS: In order to make the best decision about recommendations on immunization practices, better quality surveillance data are required. In Brazil, MenC was responsible for about 2,000 cases per year during the last 10 years. New conjugate vaccines against MenC are very effective and immunogenic, and they should be recommended, especially for children less than 5 years old. Polysaccharide vaccines should be indicated only in epidemic situations and for high-risk groups. Until new vaccines against MenC and MenB are available for routine immunization programs, the most important measure for controlling meningococcal disease is early diagnosis of these infections in order to treat patients and to offer chemoprophylaxis to contacts