Estandarización de un procedimiento espectrofotométrico para la cuantificación de polisacárido capsular de Neisseria meningitidis serogrupo X / Standardization of a spectrophotometric procedure for the quantification of Neisseria meningitidis serogroup X capsular polysaccharide

En el presente trabajo se realiza la estandarización del procedimiento espectrofotométrico de determinación de polisacárido capsular e intermedios de Neisseria meningitidis serogrupo X, mediante la determinación de los grupos fosfodiéster presentes en su estructura, por el método de Chen. Se realizó un análisis de los siguientes criterios para la estandarización: linealidad, precisión (repetibilidad y precisión intermedia) y exactitud. Se demostró mediante el diseño experimental y los procedimientos estadísticos empleados que el método es lineal (r > 0,99), el coeficiente de variación del factor respuesta < 5 por ciento, la desviación estándar relativa de la pendiente < 2 por ciento, no existiendo diferencia estadísticamente significativa entre el intercepto de la ecuación con respecto a cero; exacto, porque no existe diferencia estadísticamente significativa entre la concentración determinada en un material de trabajo y su concentración nominal; también demostró ser repetible, pues el coeficiente de variación de las concentraciones de la muestra evaluada (2,44; 2,43; 0,88 por ciento para las concentraciones bajas, medias y altas, respectivamente) es inferior al 3 por ciento y no existen diferencias estadísticamente significativas entre las medias de los resultados obtenidos por dos analistas, evaluados durante cuatro días a tres niveles de concentración. La precisión intermedia es satisfactoria(AU)

The present work comprises the standardization a spectrophotometric procedure for assessing Neisseria meningitidis, serogroup X capsular polysaccharide and their intermediates of modification, the phosphodiesters groups present in its structure, based on Chen method. An analysis of the following standardization criteria was performed: linearity, precision (repeatability and intermediate precision) and accuracy. It was demonstrated through the experimental design and the statistical procedures used that the method is linear (r > 0.99), the coefficient of variation of the response factor < 5 percent, the relative standard deviation of the slope < 2 percent, with no statistically significant difference between the intercept of the equation with respect to zero; exact, because there is no statistically significant difference between the concentration determined in a work material and its nominal concentration; it also proved to be repeatable, because the coefficient of variation of the concentrations of the sample (2.44; 2.43; 0.88 percent for low, medium and high concentrations respectively) is less than 3 percent and there is no statistically significant difference between the means of the results obtained by two analysts, evaluated for four days at three concentration levels. Its intermediate precision was satisfactory(AU)

Aislamiento de Neisseria meningitidis en muestra anorectal en hombre que tiene sexo con hombre con uretritis y sifilis primaria / Isolation of Neisseria meningitidis in anorectal specimen in a men who have sex with men with uretritis and primary syphilis

Resumen Neisseria meningitidis es una bacteria gramnegativa asociada frecuentemente a enfermedades invasoras de elevada mortalidad. Si bien su reservorio natural es la nasofaringe humana, en los últimos años han aumentado los aislamientos de este agente en la mucosa anorectal, principalmente en hombres que tienen sexo con hombres (HSH). Presentamos el caso de un HSH con infección por VIH, que consultó por un cuadro de uretritis y sifilis primaria, en el cual se aisló N. meningitidis en una muestra anorectal. Fue tratado en forma empírica con ceftriaxona y azitromicina, realizándose un cultivo de control post-tratamiento que fue negativo. A pesar del aumento de las infecciones y colonizaciones anogenitales por N. meningitidis, se desconoce su rol como patógeno genital, en la transmisión de otras infecciones y la necesidad de esquemas terapéuticos específicos.

Abstract Neisseria meningitidis is a Gram-negative bacterium frequently associated with invasive diseases with high mortality. Although its natural reservoir is the human nasopharynx, in recent years there have been increasing reports of isolation of this agent in the anorectal mucosa, mainly in men who have sex with men (MSM). We present the case of an HIV-positive MSM who consulted for urethritis and primary syphilis, in which N. meningitidis was isolated in an anorectal specimen. He was treated empirically with ceftriaxone and azithromycin, and a post-treatment control culture was negative. Despite the increase in anogenital infections and colonization by N. meningitidis, its role is unknown as a genital pathogen and in the transmission of other infections and the need for specific therapeutic regimens.

Serogrupos y resistencia antimicrobiana de Neisseria meningitidis causantes de enfermedad invasiva en Paraguay

RESUMEN La enfermedad meningocócica representa un problema de salud pública y una de las principales causas de morbilidad y mortalidad en todo el mundo. Los serogrupos que causan la mayor carga de enfermedad a nivel global son A, B, C, W e Y. El objetivo del estudio fue describir los serogrupos y la resistencia antimicrobiana de Neisseria meningitidis aisladas de enfermedad invasiva en Paraguay durante el periodo 2010-2020. Se estudiaron todas las muestras de líquido cefalorraquídeo y sangre con aislamientos o detección de ADN por PCR de N. meningitidis de pacientes de diversas edades, que fueron remitidas al Laboratorio Central de Salud Pública durante el periodo 2010-2020, dentro del marco de la vigilancia epidemiológica de meningitis (n=163) en Paraguay. La mayor frecuencia de hallazgos de N. meningitidis se observó en el grupo de edad de < 1 año. El 25,7% de los casos correspondió al serogrupo B, el 52,1% al serogrupo C, 18,4% al serogrupo W y 3,7% al serogrupo Y. En el 2018, se evidenció la mayor cantidad de casos por serogrupo C (n=27). La menor frecuencia de sensibilidad disminuida a penicilina G fue en el 2010 (12,5%) y la mayor en el 2014 (100,0%). Se registró un aumento de casos por serogrupo C a partir del 2017, posicionándose como serogrupo prevalente hasta el 2020, y además, un aumento de la sensibilidad disminuida a la penicilina. La vigilancia es de importancia en el control de la enfermedad meningocócica para detección de brotes, estimación de la carga de enfermedad, análisis de resistencia antimicrobiana, distribución de serogrupos y evaluaciones de estrategias de control.

ABSTRACT Meningococcal disease represents a public health problem and one of the main causes of morbidity and mortality worldwide. The serogroups that cause the highest burden of disease globally are A, B, C, W, and Y. The aim of the study was to describe serogroups and antimicrobial resistance of Neisseria meningitidis isolated from invasive disease in Paraguay during the 2010-2020 period. Samples of cerebrospinal fluid and blood with isolates or detection of DNA by PCR of N. meningitidis from patients of different ages referred to the Central Public Health Laboratory during the period 2010-2020 within the framework of the epidemiological surveillance of meningitis (n = 163) in Paraguay were studied. The highest frequency of N. meningitidis findings was observed in the <1 year age group, 25.7% of the cases corresponded to serogroup B, 52.1% to serogroup C, 18.4% to serogroup W and 3.7% to serogroup Y. In 2018, the highest number of cases by serogroup C (n = 27) was found. The lowest frequency of decreased sensitivity to penicillin G was in 2010 (12.5%) and the highest in 2014 (100.0%). There was an increase in cases due to serogroup C in 2017, positioning itself as the prevalent serogroup until 2020, in addition, there was an increase in decreased sensitivity to penicillin. Surveillance is important in the control of meningococcal disease for outbreak detection, estimation of the burden of disease, analysis of antimicrobial resistance, serogroup distribution, and evaluations of control strategies.

Antimicrobial susceptibility and serotypes of Neisseria meningitidis and Streptococcus pneumoniae in Sri Lanka: Experience from the National Reference Laboratory

Objective: To determine the antimicrobial susceptibility and serotypes of Neisseria (N.) meningitidis and Streptococcus (S.) pneumoniae in Sri Lankan patients. Methods: We retrospectively analyzed 11 blood culture specimens from suspected patients with invasive meningococcal disease and 26 S. pneumoniae clinical isolates. We tested 6 antimicrobials against N. meningitidis and 12 antimicrobials against S. pneumoniae. Meningococcal serogroup was determined by realtime PCR and Quellung serotyping was used for pneumococcal analysis. Results: N. meningitidis serogroup B was the most common in this study. Intermediate-susceptibility to penicillin was seen in 75.0% (6/8) of strains. Susceptibility to ciprofloxacin, levofloxacin and cotrimoxazole was 62.5% (5/8), 62.5% (5/8) and 87.5% (7/8), respectively. Excellent susceptibility was seen in cefotaxime and meropenem. In S. pneumoniae, the most common serotype was 19F in both invasive and non-invasive pneumococcal diseases. The majority of strains showed multidrug resistance. Penicillin non-susceptibility in non-meningeal strains were 13.6% and all meningeal strains were penicillin resistant. Erythromycin was highly resistant in both groups. Amoxicillin showed excellent susceptibility in non-invasive pneumococcal diseases strains. Linezolid, levofloxacin and vancomycin showed 100.0% susceptibility in all pneumococcal isolates. Conclusions: Implementation of vaccines should be considered, especially for children and high-risk populations. This may contribute to reducing pneumococcal and meningococcal invasive disease burden and help prevent emergence of antimicrobial resistant strains.

Characterisation of Neisseria meningitidis cc11/ET-15 variant by whole genome sequencing

BACKGROUND Neisseria meningitidis strains belonging to clonal complex 11 is the cause of numerous outbreaks and epidemics in the United States, Canada and Europe, accounting for 49.5% of cases of meningococcal disease caused by serogroup C worldwide. In Brazil, it is the second most frequent clonal complex within this serogroup. The genetic characterisation of cc11/ET-15 variants is important for the epidemiological monitoring of meningococcal disease, through the identification of circulating epidemic clones, to support specific actions of Health Surveillance aiming outbreaks control. OBJECTIVES The objective of this study was to identify features in the genome of cc11/ET-15 clones through whole-genome sequencing (WGS), that differ from cc11/non-ET-15 strains that could explain their virulence. METHODS The whole genome of three cc11/ET-15 representative strains were sequenced with a minimum coverage of 100X with the MiSeq System and compared to the genome of cc11/non-ET-15 strains. RESULTS Genome analysis of cc11/ET-15 variants showed the presence of resistance factors, mobile genetic elements and virulence factors not found in cc11/non-ET-15 strains. MAIN CONCLUSIONS Our results show that these strains carry virulence factors not identified in cc11/non-ET-15 strains, which could explain the high lethality rates attributed to this clone worldwide.

Neisseria meningitidis aislada de muestras de hombres que tienen sexo con hombres / Neisseria meningitidis isolated from patients in men who have sex with men

Resumen En los períodos 2000-2004 y 2014-2015 se investigó la presencia de Neisseria meningitidis en 1.143 y 544 hombres que tienen sexo con hombres respectivamente, atendidos en el marco de un programa de enfermedades de transmisión sexual. Se determinó la prevalencia de este agente, su distribución en serogrupos y su sensibilidad a los antimicrobianos. Se obtuvieron hisopados faríngeos, rectales y uretrales, que se sembraron en medio selectivo Thayer Martin modificado. La identificación se realizó mediante pruebas bioquímicas convencionales y por espectrometría de masas (MALDI-TOF). En el segundo período estudiado, sobre 85 aislamientos procedentes de faringes se investigaron los serogrupos B, C, W e Y mediante PCR. Se determinó la CIM de penicilina, ceftriaxona, rifampicina, azitromicina y ciprofloxacina en 66 aislamientos obtenidos en el primer período y en 102 logrados en el segundo. La prevalencia de N. meningitidis fue del 17,8% en el primer período y del 28,1% en el segundo; este microorganismo se aisló más frecuentemente de fauces. Los serogrupos hallados fueron B (31,5%), Y (7,6%) y W (3,3%), con un 9,8% de aislamientos no capsulados; los restantes corresponderían a otros serogrupos. El 34,8% y el 63,7% de los aislados estudiados correspondientes al primer y segundo período, respectivamente, tuvieron sensibilidad intermedia a la penicilina, y un 11,8% de los evaluados en el segundo período fueron resistentes a dicho antibiótico. Todos los aislados estudiados fueron sensibles a ceftriaxona y a ciprofloxacina (excepto 3, con CIM entre 0,25 y 0,5(g/ml), el 3% fueron resistentes a rifampicina y el 2% fueron no sensibles a azitromicina. La portación de N. meningitidis en hombres que tienen sexo con hombres fue elevada y hubo un alto porcentaje de cepas no sensibles a penicilina. El serogrupo B fue prevalente.

Abstract During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5(g/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.

Impacto do uso da reação em cadeia da polimerase para o diagnóstico de meningite bacteriana em substituição a contraimunoeletroforese / Impact of using polymerase chain reaction for the diagnosis of bacterial meningitis in substitution for counterimmunoelectrophoresis

Introdução: a meningite bacteriana é um grave problema de Saúde Pública mundial, tendo como principais agentes: Neisseria meningitidis, Streptococcus pneumoniae e Haemophilus influenzae. A metodologia de diagnóstico empregada no Instituto Adolfo Lutz ­ Centro de Laboratório Regional Santo André até o ano de 2011 era a contraimunoeletroforese (CIE), depois foi substituída pela reação em cadeia da polimerase em tempo real (qPCR), que apresenta maior sensibilidade. Objetivo: este trabalho objetivou comparar ambas as metodologias no período de 2009 a 2018, para avaliação do impacto da introdução da qPCR no diagnóstico das meningites bacterianas nos 7 municípios da região do ABC do Estado de São Paulo. Metodologia: foram avaliadas a quantidade total de exames realizados, a média mensal, a positividade no período, os municípios requisitantes e a prevalência das bactérias causadoras de meningite, no período de abril/2009 até dezembro/2018. Resultados: Foram 377 exames de CIE e 1305 de qPCR, com média anual de 230 exames em 2010-2013 e 130 exames em 2014-2018. Observou-se aumento da positividade entre as técnicas, 17,8% para CIE e 33,8% para qPCR. N. meningitidis foi responsável pela maioria dos casos entre 2011 e 2013, cerca de 61% dos casos positivos, enquanto que entre 2014 e 2018 foi S. pneumoniae, cerca de 53%. Conclusão: os resultados indicaram que a qPCR foi mais eficiente em detectar os agentes causadores de meningite bacteriana na região do que a técnica de CIE. Por fim, este trabalho suporta a implantação da metodologia de qPCR para diagnóstico de meningite em substituição de técnicas menos sensíveis.

Introduction: bacterial meningitis is still a serious worldwide public health problem, and the main etiological agents are: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. The diagnostic methodology employed at the Adolfo Lutz Institute ­ Santo André Regional Laboratory Center until 2011 was the ounterimmunoelectrophoresis (CIE), then it was replaced by the real-time polymerase chain reaction (qPCR), which is more sensitivity. Objective: this study aimed to compare both methodologies from 2009 to 2018 to evaluate the impact of the introduction of qPCR in the diagnosis of bacterial meningitis in the 7 cities of the ABC region of São Paulo State. Methodology: the total number of tests performed, the month average, the positivity in the period, the requesting cities and the prevalence of bacteria causing meningitis were evaluated from April/2009 to December/2018. Results: there were 377 CIE exams and 1305 qPCR exams, with an annual average of 230 exams in 2010-2013 and 130 exams in 2014-2018. There was an increase in positivity between the performed techniques, 17.8% for CIE and 33.8% for qPCR. N. meningitidis accounted for most cases of bacterial meningitis between 2011 and 2013, about 61% of positive cases, whereas between 2014 and 2018 it was S. pneumoniae, with about 53%. Conclusion: the results indicated that qPCR was more efficient in detecting the agents that cause bacterial meningitis in the region than the CIE technique. Finally, this work supports the implementation of qPCR methodology for diagnosis of meningitis in replacement of less sensitive techniques.

Vacuna cubana antimeningocócica VA-MENGOC-BC®: Treinta años de uso y potencialidades vigentes / Cuban Meningococcal Vaccine VA-MENGOC-BC®: 30 Years of Use and Future Potential

La enfermedad meningocócica provoca cada año más de 500.000 casos y 85.000 muertes en el mundo y un 20 por ciento de los sobrevivientes sufre secuelas. En Cuba, en 1980, la incidencia llegó a 14,4 por 100.000 habitantes para todas las edades y fue declarada como el principal problema de salud del país. En niños menores de 1 año se reportaron más de 120 casos por 100.000 habitantes en algunas provincias. En 1989, investigadores en La Habana, Cuba desarrollaron una vacuna contra meningococo B y C; VA-MENGOC-BC®, la primera en el mundo eficaz contra el meningococo del serogrupo B. Su eficacia de 83 por ciento se demostró en un estudio de campo prospectivo a doble ciegas, aleatorizado, contra placebo. En su producción se empleó por primera vez la tecnología vesicular o proteoliposómica. Esta vacuna se usó en una campaña de vacunación masiva y posteriormente fue incluida en el Programa Ampliado de Inmunización en Cuba y tuvo un impacto acumulado sobre la incidencia de la enfermedad meningocócica del serogrupo B superior a 95 por ciento (93 por ciento-98 por ciento). La vacunación masiva y sistemática cambió el espectro de cepas del meningococo en los portadores asintomáticos sanos y la circulación de cepas en las poblaciones hacia fenotipos no virulentos. La enfermedad dejó de ser un problema de salud en el país. VA-MENGOC-BC® es la vacuna contra la enfermedad meningocócica del serogrupo B que se aplicó en el mayor número de susceptibles en el mundo. En América Latina se administraron más de 60 millones de dosis. En varios países donde se ha usado VA-MENGOC-BC®, circulan cepas diferentes a la vacunal y contra todas ellas se demostró un elevado porcentaje de efectividad (55%-98 por ciento en menores de 4 años y 73 por ciento-100 por ciento en mayores de 4 años). VA-MENGOC-BC® y su tecnología proteoliposómica han tenido impacto y mantienen su potencialidad, no solo en la enfermedad meningocócica, sino en el desarrollo de otras vacunas y adyuvantes(AU)

Every year, meningococcal infection by Neisseria meningitidis causes over 500,000 cases and 85,000 deaths in the world, with 20 percent of survivors suffering sequelae. In Cuba its incidence in 1980 reached 5.9 cases per 100,000 population; about 80 percent of cases were serogroup B, prompting health authorities to declare meningococcal disease the country's main public health problem. Several provinces reported over 120 cases per 100,000 children aged <1 year, overwhelmingly serogroup B. At that time, no vaccines existed with proven efficacy against N. meningitidis serogroup B, nor was there a vaccine candidate that could be successful in the short term. By 1989, researchers in Havana had developed a Cuban meningococcal B and C vaccine, VA-MENGOC-BC®, the world's first against serogroup B meningococcal disease. Its efficacy of 83 percent was demonstrated in a prospective, randomized, double-blind, placebo-controlled field study. Vaccine production used vesicle or proteoliposome technology for the first time. The same year, the World Intellectual Property Organization awarded its gold medal to the main authors of the VA-MENGOC-BC® patent. The vaccine was used in a mass vaccination campaign and later included in Cuba's National Immunization Program, with a cumulative impact on incidence of serogroup B meningococcal disease greater than 95 percent (93 percent-98 percent). Mass, systematic vaccination shifted the spectrum of meningococcal strains in healthy asymptomatic carriers and strains circulating among population groups toward nonvirulent phenotypes. The disease ceased to be a public health problem in the country. VA-MENGOC-BC® is the most widely applied vaccine against serogroup B meningococcal disease in the world. Over 60 million doses have been administered in Latin America. In several countries where it has been applied, in which strains other than the vaccine-targeted strains circulate, VA-MENGOC-BC® has demonstrated effectiveness against all (55 percent-98 percent in children aged ≥4 years and 73 percent-100 percent in children aged >4 years). The vaccine and its proteoliposome technology have had an impact and continue to have potential, not only for meningococcal disease, but also for development of other vaccines and adjuvants(AU)

Carriage prevalence of Neisseria meningitidis in the Americas in the 21st century: a systematic review

Abstract Neisseria meningitidis is a bacterium that colonizes the human nasopharynx and is transmitted by respiratory droplets from asymptomatic or symptomatic carriers. Occasionally, the pathogen invades the mucosa and enters the bloodstream, causing invasive meningococcal disease, a life-threatening infection. While meningococcal colonization is the first step in the development of invasive disease, the risk factors that predict progression from asymptomatic to symptomatic status are not well-known. The present report aimed to describe the prevalence of N. meningitidis carriers throughout the Americas, emphasizing the risk factors associated with carrier status, as well as the most prevalent serogroups in each studied population. We conducted a systematic review by searching for original studies in the MEDLINE/PubMed, Embase, LILACS and SciELO databases, published between 2001 and 2018. Exclusion criteria were articles published in a review format, case studies, case control studies, investigations involving animal models, and techniques or publications that did not address the prevalence of asymptomatic carriers in an American country. A total of 784 articles were identified, of which 23 were selected. The results indicate that the highest prevalence rates are concentrated in Cuba (31.9%), the United States (24%), and Brazil (21.5%), with increased prevalence found among adolescents and young adults, specifically university students and males. The present systematic review was designed to support epidemiological surveillance and prevention measures to aid in the formulation of strategies designed to control the transmission of meningococci in a variety of populations and countries throughout the Americas.

Experts' consensus on immunization with meningococcal vaccines in China / 中华流行病学杂志

Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine,meningococcal polysaccharide conjugate vaccine,and a combined vaccine.Meningococcal conjugate vaccines immunization schedules vary by vaccine manufacturer,and often cause confusion in immunization practices.Based on the epidemiological characteristics of meningococcal disease,serogroup distribution of Neisseria meningitidis,and research progress on the immunogenicity and safety of meningococcal vaccines,we developed an experts' consensus on immunization with meningococcal vaccines to provide guidance for immunization providers and for centers for disease control and prevention staff.

A meningococcal B vaccine induces cross-protection against gonorrhea

PURPOSE: Neisseria meningitidis and Neisseria gonorrhoeae share between 80% and 90% of their genetic sequence. Meningococcal serogroup B vaccines based on outer membrane vesicles—such as VA-MENGOC-BC—could cross-protect against gonorrhea. The aim of this study was to analyze the incidence rates of gonorrhea and other sexually transmitted diseases with respect to the use of the VA-MENGOC-BC vaccine. MATERIALS AND METHODS: Health statistics between 1970 and 2017 were reviewed and the incidence of meningococcal disease and sexually transmitted diseases (gonorrhea, syphilis, condyloma acuminatum, hepatitis B and human immunodeficiency virus infection) were analyzed during the pre- and post-vaccination periods. Gonorrhea incidence was also analyzed by age groups. RESULTS: VA-MENGOC-BC was successfully used to control a meningococcal epidemic in Cuba. The strategy to combat the epidemic was carried out in two stages. The first one was a nationwide mass-vaccination campaign from 1989 to 1990, targeting the population at highest-risk aged 3 months to 24 years. During the second stage, begun in 1991, it was included in the Expanded Immunization Program. Gonorrhea incidence increased from 1970 to 1989. However, after the VA-MENGOC-BC massive vaccination campaign a sharp decrease of gonorrhea incidence was observed. It lasted between 1989 and 1993. A second incidence peak was detected in 1995, but it dropped again. Data clearly show a decline in the incidence of gonorrhea following massive vaccination, in contrast with other sexually transmitted diseases. Incidence rates in unvaccinated age groups also decreased, probably due to herd immunity. CONCLUSION: There is evidence that VA-MENGOC-BC could induce a moderate protection against gonorrhea.

Acute meningitis and encephalitis syndrome surveillance disease burden in four China prefectures / 中华预防医学杂志

Objectives@#To explore acute meningitis and encephalitis syndrome (AMES) surveillance in 4 China prefectures, to understand the epidemiological features and disease burden of neisseria meningitides (Nm) meningitis, streptococcus pneumoniae (Sp) meningitis, haemophilus influenza type b (Hib) meningitis and Japanese encephalitis and provide evidence for related disease prevention and control.@*Methods@#AMES surveillance were conducted in Jinan, Shandong Province and Yichang, Hubei Province in September 2006, and in 13 districts of Shijiazhuang, Hebei Province and Guigang City, Guangxi Zhuang Autonomous Region in April 2007. Six hospitals in each city were selected as monitoring pilot hospitals to carry out reports of suspected cases of acute meningitis and encephalitis, case investigation, blood specimens and cerebrospinal fluid specimen collection, anti-JEV IgM antibody enzyme-linked immunosorbent assay, Nm, Sp and Hib culture and polymerase chain reaction detection, etc. According to the age group, the incidence of bacterial meningitis and Japanese encephalitis in local residents <20 years old was estimated.@*Results@#From 2006 to 2013, a total of 19 423 surveillance cases were reported in four cities, of which 11 071 (56.99%) were reported in the pilot hospitals. Of the 11 071 cases, 5 315 were tested for bacteriology and 9 180 were tested for anti-JEV IgM antibodies. Among the bacteriological tests, 176 cases were positive, including 75 cases of Nm positive, 91 cases of Sp positive and 10 cases of Hib positive. The incidence of three bacterial meningitis is estimated for people under 20 years old, with estimated incidence of Nm, Sp and Hib meningitis in children <5 years old was 0.46/100 000-0.71/100 000, 0.34/100 000-0.83/100 000 and 0.32/100 000-0.57/100 000 respectively; the estimated incidence of Nm and Sp meningitis in children aged 5-9 years was 0.59/100 000-1.14/100 000 and 0.50/100 000-1.66/100 000 respectively. In 732 cases of positive JE cases, the positive detection rates of <5 years old, 40-49 years old and ≥50 years old were 9.51% (95/999), 28.09% (66/235) and 33.85% (130/384), respectively. The estimated annual incidence rate of JE was 0.12/100 000-0.79/100 000.ratio of cases 1.19∶1. Most of cases (27.30%) were children and adolescents aged 5-14 years and those (26.84%) aged over 45 year.@*Conclusion@#The study found that primary and secondary school students are the key population of Nm meningitis, suggesting that it is necessary to explore the enhanced immunization study of meningococcal vaccine in this population; Sp has the possibility of occurrence in all age groups; <5 years old children are the main population of Hib meningitis.

Analysis of epidemic characteristics for meningococcal meningitis in China during 2015-2017 / 中华预防医学杂志

Objective@#To analyze the characteristics of epidemiology and neisseria meningitidis (Nm) serogroups distribution for meningococcal meningitis (MM) cases in China from 2015 to 2017.@*Methods@#The data of MM cases were collected from National Notifiable Diseases Registry System (NNDRS) and case-based MM surveillance system (MMSS) from 2015 to 2017; Demographic data are from the National Bureau of statistics. Inclusion criteria: the date of onset was January 1, 2015 to December 31, 2017, the status of infectious disease report card was "final examination card", the cases are classified as "laboratory confirmed cases" and "clinical diagnostic cases", and the card data information of disease name was "Meningococcal meningitis". According to the Diagnostic Criteria for Meningococcal meningitis (WS295-2008), laboratory confirm was made for reported cases or clinically diagnosed cases of meningococcal meningitis.@*Results@#From 2015 to 2017, a total of 325 MM cases were reported in China, with an average annual incidence of 0.007 9 per 100 000 population. And 148 cases were laboratory confirmed. There were 3, 15, 12, 5, 2 and 18 provinces which were reported serogroup A, B, C, W, Y, Others and NG MM Cases, respectively. Except for Tibet and Hainan, other provinces have reported group A cases; The provinces reporting group B, C, W and Y cases increased by 9, 11, 13 and 2 provinces in 2007, respectively compared with 2005. Serogroup B was the primary reason causing the cases of <1 year old and 1-6 years old children; and in this age group, 51.43% (18 cases) and 68.18% (15 cases) of group B were accounted for in laboratory confirmed, respectively; Serogroup C, others and NG was the major reason in the cases of 7-12 and >12 years old students and adults: 33.33% (5 cases) and 26.32% (20 cases) of group C were accounted for in laboratory confirmed respectively, then 26.67% (4 cases) and 34.21% (26 cases) of group others and NG were accounted for respectively; 2 cases of serogroup Y were all >12 years old.@*Conclusion@#The epidemic serogroup of Nm caused MM cases showed a diversifying trend. To develop and provide new vaccines for serogroup B and other bacteria groups should be one of the important tasks for MM control and prevention in the future.

Molecular characteristics of serogroup B neisseria meningitidis, China / 中华预防医学杂志

Objective@#To investigate the molecular characteristics of serogroup B neisseria meningitidis in China.@*Methods@#Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed.@*Results@#The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types.@*Conclusion@#CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.

Experts′ consensus on immunization with meningococcal vaccines in China / 中华预防医学杂志

Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine, meningococcal polysaccharide conjugate vaccine, and a combined vaccine. Meningococcal conjugate vaccines immunization schedules vary by vaccine manufacturer, and often cause confusion in immunization practices. Based on the epidemiological characteristics of meningococcal disease, serogroup distribution of Neisseria meningitidis, and research progress on the immunogenicity and safety of meningococcal vaccines, we developed an experts′ consensus on immunization with meningococcal vaccines to provide guidance for immunization providers and for centers for disease control and prevention staff.

Experts' consensus on immunization with meningococcal vaccines in China / 中华流行病学杂志

Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine,meningococcal polysaccharide conjugate vaccine,and a combined vaccine.Meningococcal conjugate vaccines immunization schedules vary by vaccine manufacturer,and often cause confusion in immunization practices.Based on the epidemiological characteristics of meningococcal disease,serogroup distribution of Neisseria meningitidis,and research progress on the immunogenicity and safety of meningococcal vaccines,we developed an experts' consensus on immunization with meningococcal vaccines to provide guidance for immunization providers and for centers for disease control and prevention staff.

Genotipos de Neisseria meningitidis aislados de pacientes con enfermedad meningocócica en Paraguay, 1996-2015 / Genotypes of Neisseria meningitidis isolates in patients with meningococcal meningitis in Paraguay, 1996-2015 / Genótipos de Neisseria meningitidis isolados de pacientes com doença meningocócica no Paraguai, 1996-2015

RESUMEN Objetivo Describir las características fenotípicas y genotípicas de cepas de Neisseria meningitidis aisladas de enfermedad meningocócica en Paraguay entre 1996 y 2015. Métodos Se estudiaron por métodos microbiológicos convencionales y técnicas moleculares 114 aislamientos de N. meningitidis y 12 muestras clínicas sin aislamiento confirmadas por reacción en cadena de la polimerasa (PCR) que fueron remitidas por los diferentes centros centinelas y centros colaboradores de Paraguay. Resultados El grupo de edad más afectado fue el de menores de 1 año (19,0%), seguido por el de 1 a 5 años (17,5%). Un mayor porcentaje de las cepas se aisló de casos de meningitis (81,7%) y el serogrupo B se encontró en 60,3% de los casos. Los fenotipos más frecuentes fueron B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST y W:NT:P1.2 (10,5%), respectivamente. Los complejos clonales prevalentes fueron ST-11/ET37 complex 29,6% (8/27) con predominio del serogrupo W (6/8), ST-35 complex 18,5% (5/27) en el serogrupo B (4/4), y ST-32/ET5 complex 14,8% (4/16) en el serogrupo B (5/5). Conclusiones En Paraguay la enfermedad meningocócica es relativamente infrecuente. Los análisis de distribución de serogrupo muestran que el más frecuente es el B y en los últimos dos años aumentaron los casos de enfermedad meningocócica por C y W. Los complejos clonales encontrados se correlacionan con los hallados en la región del Cono Sur. Debido al alto nivel de virulencia de N. meningitidis, su vigilancia debe constituir una prioridad estratégica de los sistemas de salud pública nacionales y regionales para prevenir brotes epidémicos y apoyar la toma de decisiones en salud pública.

ABSTRACT Objective Describe the phenotypical and genotypical characteristics of Neisseria meningitidis isolates from cases of meningococcal disease in Paraguay between 1996 and 2015. Methods Conventional microbiological methods and molecular techniques were used to study 114 isolates of N. meningitidis and 12 clinical samples without isolation (confirmed by polymerase chain reaction), provided by various sentinel centers and collaborating centers in Paraguay. Results The most affected age group was children under 1 year (19.0%), followed by 1-5-year-olds (17.5%). The highest percentage of strains was isolated in meningitis cases (81.7%) and serogroup B was found in 60.3% of cases. The most frequent phenotypes were B:4:p1.14 (16.0%), B:15:p1.5, C:nt:nst, and W:nt:p1.2 (10.5%), respectively. The prevalent clonal complexes were: ST-11/ET37 complex, 29.6% (8/27), predominantly serogroup W (6/8); ST-35 complex, 18.5% (5/27), in serogroup B (4/4); and ST-32/ET5 complex, 14.8% (4/16), in serogroup B (5/5). Conclusions Meningococcal meningitis is relatively uncommon in Paraguay. Distribution analysis showed that serogroup B is the most common and that the number of cases of meningococcal disease caused by serogroups C and W increased in the last two years. The identified clonal complexes were correlated with those found in the Southern Cone region. Due to the high virulence of N. meningitidis, its surveillance should be a strategic priority of national and regional public health systems to prevent epidemic outbreaks and support public health decision-making.

RESUMO Objetivo Descrever as características fenotípicas e genotípicas de cepas de Neisseria meningitidis isoladas de casos de doença meningocócica no Paraguai entre 1996 e 2015. Métodos Foram estudados por métodos microbiológicos convencionais e técnicas moleculares 114 isolados de N. meningitidis e 12 amostras clínicas sem isolamento confirmadas por reação em cadeia da polimerase (PCR) enviados por diferentes centros-sentinela e centros colaboradores do Paraguai. Resultados A faixa etária mais afetada foi a de crianças menores de 1 ano (19,0%) e crianças de 1 a 5 anos (17,5%). Uma maior porcentagem de cepas foi isolada de casos de meningite (81,7%) e o sorogrupo B foi identificado em 60,3% dos casos. Os fenótipos mais comuns foram B:4:P1.14 (16,0%), B:15:P1.5, C:NT:NST e W:NT:P1.2 (10,5%), respectivamente. Os complexos clonais mais prevalentes foram o complexo ST-11/ET37 (29,6%, 8/27) com predomínio no sorogrupo W (6/8), complexo ST-35 (18,5%, 5/27) no sorogrupo B (4/4) e complexo ST-32/ET5 (14,8%, 4/16) no sorogrupo B (5/5). Conclusões A doença meningocócica é relativamente pouco comum no Paraguai. A análise da distribuição dos sorogrupos demonstrou que o sorogrupo B é o mais prevalente e, nos últimos dois anos, ouve um aumento nos casos de doença meningocócica pelos sorogrupos C e W. Os complexos clonais encontrados se correlacionam com os achados na região do Cone Sul. Devido à alta virulência da N. meningitidis, a vigilância deste agente deve ser uma prioridade estratégica dos sistemas de saúde pública nacionais e regionais para prevenir surtos epidêmicos e subsidiar a tomada de decisão em saúde pública.

Cellulitis: An unusual manifestation of Neisseria meningitidis infection

@#Introduction: Neisseria meningitidis infections often cause severe meningitis as well as bacteraemia. However, cellulitis in meningococcal diseases have rarely been described. Here, we report a case of right lower limb cellulitis caused by N. meningitidis. Case Report: A 69-year-old woman presented with fever and lower limb swelling. She had diabetes mellitus, hypertension, dyslipidaemia and a history of surgical resection of vulvar carcinoma. N. meningitidis was isolated from her blood culture. Discussion: This report provides additional evidence in support of N. meningitidis as a cause of cellulitis.

Experts' consensus on immunization with meningococcal vaccines in China / 中华预防医学杂志

Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine, meningococcal polysaccharide conjugate vaccine, and a combined vaccine. Meningococcal conjugate vaccines immunization schedules vary by vaccine manufacturer, and often cause confusion in immunization practices. Based on the epidemiological characteristics of meningococcal disease, serogroup distribution of Neisseria meningitidis, and research progress on the immunogenicity and safety of meningococcal vaccines, we developed an experts' consensus on immunization with meningococcal vaccines to provide guidance for immunization providers and for centers for disease control and prevention staff.

Coinfección por astrovirus y Neisseria meningitidis serogrupo B en una niña / Coinfection by astrovirus and Neisseria B meningitidis in a girl

La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.

Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.