Asunto(s)
Bacteriemia/microbiología , Infecciones Meningocócicas/microbiología , Neisseria meningitidis Serogrupo W-135/patogenicidad , Anciano , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Comorbilidad , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Susceptibilidad a Enfermedades , Farmacorresistencia Bacteriana Múltiple , Sustitución de Medicamentos , Femenino , Humanos , Infecciones Meningocócicas/diagnóstico , Infecciones Meningocócicas/tratamiento farmacológico , Neisseria meningitidis Serogrupo W-135/efectos de los fármacos , Neisseria meningitidis Serogrupo W-135/aislamiento & purificación , Infecciones del Sistema Respiratorio/diagnóstico , Sepsis/diagnósticoRESUMEN
The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.
Asunto(s)
Brotes de Enfermedades , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/microbiología , Neisseria meningitidis Serogrupo W-135/genética , Neisseria meningitidis Serogrupo W-135/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Genes Bacterianos , Genoma Viral , Genotipo , Salud Global , Humanos , Epidemiología Molecular , Neisseria meningitidis Serogrupo W-135/clasificación , Neisseria meningitidis Serogrupo W-135/patogenicidad , Filogenia , Escocia/epidemiología , Serogrupo , Serotipificación , Suecia/epidemiología , Viaje , Virulencia/genéticaRESUMEN
We report on the case of fatal "purpura fulminans" caused by Neisseria meningitidis W135 that occurred in a young French soldier vaccinated a few months earlier with the tetravalent conjugate vaccine ACYW135. Biological investigations revealed adequate titers of postvaccination antibodies against serogroups A, C, and W135 and led to the post-mortem diagnosis of a complete C7 complement deficiency. Late complement component deficiency is a well-known risk factor of meningococcal diseases, but usually exposes to recurrent mild infections, whereas severe invasive meningococcal diseases are more likely to occur among properdin-deficient patients. Awareness of the potentially life-threatening nature of late complement component deficiency should lead to improved diagnosis among young people, especially when past medical history reveals recurrent mild infections.
Asunto(s)
Personal Militar , Púrpura Fulminante/etiología , Francia/epidemiología , Humanos , Masculino , Neisseria meningitidis Serogrupo W-135/patogenicidad , Púrpura Fulminante/complicaciones , Púrpura Fulminante/epidemiología , Púrpura Fulminante/mortalidad , Vacunación/mortalidad , Adulto JovenRESUMEN
Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis. Crucial virulence determinants of pathogenic Nm strains are the polysaccharide capsules that support invasion by hindering complement attack. In NmW-135 and NmY the capsules are built from the repeating units (â 6)-α-D-Gal-(1 â 4)-α-Neu5Ac-(2 â)n and (â 6)-α-D-Glc-(1 â 4)-α-Neu5Ac-(2 â)n, respectively. These unusual heteropolymers represent unique examples of a conjugation between sialic acid and hexosyl-sugars in a polymer chain. Moreover, despite the various catalytic strategies needed for sialic acid and hexose transfer, single enzymes (SiaDW-135/Y) have been identified to form these heteropolymers. Here we used SiaDW-135 as a model system to delineate structure-function relationships. In size exclusion chromatography active SiaDW-135 migrated as a monomer. Fold recognition programs suggested two separate glycosyltransferase domains, both containing a GT-B-fold. Based on conserved motifs predicted folds could be classified as a hexosyl- and sialyltransferase. To analyze enzyme properties and interplay of the two identified glycosyltransferase domains, saturation transfer difference NMR and mutational studies were carried out. Simultaneous and independent binding of UDP-Gal and CMP-Sia was seen in the absence of an acceptor as well as when the catalytic cycle was allowed to proceed. Enzyme variants with only one functionality were generated by site-directed mutagenesis and shown to complement each other in trans when combined in an in vitro test system. Together the data strongly suggests that SiaDW-135 has evolved by fusion of two independent ancestral genes encoding sialyl- and galactosyltransferase activity.
Asunto(s)
Cápsulas Bacterianas/metabolismo , Proteínas Bacterianas/metabolismo , Evolución Molecular , Neisseria meningitidis Serogrupo W-135/enzimología , Polisacáridos Bacterianos/biosíntesis , Sialiltransferasas/metabolismo , Cápsulas Bacterianas/química , Cápsulas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Fusión Génica/fisiología , Humanos , Meningitis Meningocócica/enzimología , Meningitis Meningocócica/genética , Meningitis Meningocócica/patología , Mutagénesis Sitio-Dirigida , Neisseria meningitidis Serogrupo W-135/genética , Neisseria meningitidis Serogrupo W-135/patogenicidad , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/genética , Estructura Terciaria de Proteína , Sepsis/enzimología , Sepsis/genética , Sepsis/patología , Sialiltransferasas/química , Sialiltransferasas/genética , Uridina Difosfato Galactosa/química , Uridina Difosfato Galactosa/genética , Uridina Difosfato Galactosa/metabolismoRESUMEN
BACKGROUND: Meningococcal epidemics in Africa are generally caused by capsular group A strains, but W-135 or X strains also cause epidemics in this region. Factor H-binding protein (fHbp) is a novel antigen being investigated for use in group B vaccines. Little is known about fHbp in strains from other capsular groups. METHODS: We investigated fHbp in 35 group A, W-135, and X strains from Africa. RESULTS: The 22 group A isolates, which included each of the sequence types (STs) responsible for epidemics since 1963, and 4 group X and 3 group W-135 isolates from recent epidemics had genes encoding fHbp in antigenic variant group 1. The remaining 6 W-135 isolates had fHbp variant 2. Within each fHbp variant group, there was 92%-100% amino acid identity, and the proteins expressed conserved epitopes recognized by bactericidal monoclonal antibodies. Serum samples obtained from mice vaccinated with native outer membrane vesicle vaccines from mutants engineered to express fHbp variants had broad bactericidal activity against group A, W-135, or X strains. CONCLUSIONS: Despite extensive natural exposure of the African population, fHbp is conserved among African strains. A native outer membrane vesicle vaccine that expresses fHbp variants can potentially elicit protective antibodies against strains from all capsular groups that cause epidemics in the region.
Asunto(s)
Proteínas del Sistema Complemento/inmunología , Meningitis Meningocócica/genética , Neisseria meningitidis Serogrupo A/patogenicidad , Neisseria meningitidis Serogrupo W-135/patogenicidad , África/epidemiología , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Factor H de Complemento/inmunología , Factor H de Complemento/metabolismo , Epítopos/química , Epítopos/inmunología , Humanos , Meningitis Meningocócica/epidemiología , Meningitis Meningocócica/inmunología , Meningitis Meningocócica/prevención & control , Neisseria meningitidis/genética , Neisseria meningitidis/aislamiento & purificación , Neisseria meningitidis/patogenicidad , Neisseria meningitidis Serogrupo A/genética , Neisseria meningitidis Serogrupo A/aislamiento & purificación , Neisseria meningitidis Serogrupo W-135/genética , Neisseria meningitidis Serogrupo W-135/aislamiento & purificación , Reacción en Cadena de la PolimerasaRESUMEN
In 2002, the largest epidemic of Neisseria meningitidis serogroup W135 occurred in Burkina Faso. The highest attack rate was in children <5 years of age. We describe cases from 1 district and evaluate the performance of the Pastorex test, which had good sensitivity (84%) and specificity (89%) compared with culture or PCR.
Asunto(s)
Brotes de Enfermedades , Meningitis Meningocócica/epidemiología , Neisseria meningitidis Serogrupo W-135/clasificación , Adolescente , Adulto , Factores de Edad , Técnicas Bacteriológicas , Burkina Faso/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Meningitis Meningocócica/líquido cefalorraquídeo , Meningitis Meningocócica/diagnóstico , Neisseria meningitidis Serogrupo W-135/aislamiento & purificación , Neisseria meningitidis Serogrupo W-135/patogenicidad , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
Although Neisseria meningitidis is a highly variable organism, most invasive disease is caused by a minority of genotypes. Hypervirulent lineages have been identified and their pandemic spread has been traced. During a longitudinal meningococcal colonization study in a district of northern Ghana clonal waves of carriage and disease were observed. Genetic diversification of genoclouds was analysed by pulsed field gel electrophoretic (PFGE) analysis of isolates from healthy carriers and from meningitis patients. Even during the limited time of persistence in the district, microevolution of the dominating genoclouds took place. Population genomic analyses are required to understand the genetic basis for the emergence of new lineages with epidemic potential, which is of crucial importance for the development of long-term global vaccination strategies against meningococcal disease.
Asunto(s)
Variación Genética , Meningitis Meningocócica/epidemiología , Neisseria meningitidis/genética , ADN Bacteriano/análisis , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Geografía , Ghana/epidemiología , Humanos , Meningitis Meningocócica/inmunología , Neisseria meningitidis/clasificación , Neisseria meningitidis/patogenicidad , Neisseria meningitidis Serogrupo A/clasificación , Neisseria meningitidis Serogrupo A/genética , Neisseria meningitidis Serogrupo A/patogenicidad , Neisseria meningitidis Serogrupo W-135/clasificación , Neisseria meningitidis Serogrupo W-135/genética , Neisseria meningitidis Serogrupo W-135/patogenicidad , Serotipificación , Factores de Tiempo , VirulenciaRESUMEN
We developed two Neisseria meningitidis multiplex PCR assays to be used consecutively that allow determination of the serogroup and capsular status of serogroup A, B, C, 29E, W135, X, and Y cnl-3/cnl-1-like-containing N. meningitidis isolates by direct analysis of the amplicon size. These assays offer a rapid and simple method of serogrouping N. meningitidis.
Asunto(s)
Neisseria meningitidis/clasificación , Neisseria meningitidis/genética , Reacción en Cadena de la Polimerasa/métodos , Serotipificación/métodos , Secuencia de Bases , Portador Sano/microbiología , Cartilla de ADN/genética , ADN Bacteriano/genética , Humanos , Infecciones Meningocócicas/microbiología , Neisseria meningitidis/patogenicidad , Neisseria meningitidis Serogrupo A/clasificación , Neisseria meningitidis Serogrupo A/genética , Neisseria meningitidis Serogrupo A/patogenicidad , Neisseria meningitidis Serogrupo B/clasificación , Neisseria meningitidis Serogrupo B/genética , Neisseria meningitidis Serogrupo B/patogenicidad , Neisseria meningitidis Serogrupo C/clasificación , Neisseria meningitidis Serogrupo C/genética , Neisseria meningitidis Serogrupo C/patogenicidad , Neisseria meningitidis Serogrupo W-135/clasificación , Neisseria meningitidis Serogrupo W-135/genética , Neisseria meningitidis Serogrupo W-135/patogenicidad , Neisseria meningitidis Serogrupo Y/clasificación , Neisseria meningitidis Serogrupo Y/genética , Neisseria meningitidis Serogrupo Y/patogenicidad , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Sensibilidad y Especificidad , Serotipificación/estadística & datos numéricos , Virulencia/genéticaRESUMEN
Since the Neisseria meningitidis serogroup W135 epidemic in Burkina Faso in 2002, the neighbouring countries dread undergoing outbreaks. Niger has strongly enhanced the microbiological surveillance, especially by adding the polymerase chain reaction (PCR) assay to the national framework of the surveillance system. During the 2003 epidemic season, 8113 clinically suspected cases of meningitis were notified and nine districts of the 42 crossed the epidemic threshold, while during the 2004 season, the number of cases was 3521 and four districts notified epidemics. In 2003 and 2004, serogroup A was identified in most N. meningitidis from cerebrospinal fluid (CSF) specimens (89.7% of 759 and 87.2% of 406, respectively). Although serogroup W135 represented only 8.3% of the meningococcal meningitis in 2003 and 7.9% in 2004, and was not involved in outbreaks, it was widespread in various areas of the country. In the regions that notified epidemics, the proportion of serogroup W135 was tiny while it exceeded 40% in several non-epidemic regions. Despite the wide distribution of W135 serogroup in Niger and the fears expressed in 2001, the threat of a large epidemic caused by N. meningitidis W135 seems to have been averted in Niger so far. There is no clear indication whether this serogroup will play a lasting role in the epidemiology of meningococcal meningitis or not. As early as in the 1990s, a significant but transient increase in the incidence of N. meningitidis serogroup X was observed. Close microbiological surveillance is crucial for monitoring the threat and for identifying at the earliest the serogroups involved in epidemics.