Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial.

Science.gov (United States)

Richmond, Peter C; Marshall, Helen S; Nissen, Michael D; Jiang, Qin; Jansen, Kathrin U; Garcés-Sánchez, Maria; Martinón-Torres, Federico; Beeslaar, Johannes; Szenborn, Leszek; Wysocki, Jacek; Eiden, Joseph; Harris, Shannon L; Jones, Thomas R; Perez, John L

2012-08-01

Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease, but a broadly protective vaccine is not currently licensed. A bivalent recombinant factor H-binding protein vaccine (recombinant lipoprotein 2086) has been developed to provide broad coverage against diverse invasive meningococcus serogroup B strains. Our aim was to test the immune response of this vaccine. This randomised, placebo-controlled trial enrolled healthy adolescents from 25 sites in Australia, Poland, and Spain. Exclusion criteria were previous invasive meningococcal disease or serogroup B vaccination, previous adverse reaction or known hypersensitivity to the vaccine, any significant comorbidities, and immunosuppressive therapy or receipt of blood products in the past 6 months. Participants were randomly assigned with a computerised block randomisation scheme to receive ascending doses of vaccine (60, 120, or 200 μg) or placebo at 0, 2, and 6 months. Principal investigators, participants and their guardians, and laboratory personnel were masked to the allocation; dispensing staff were not. Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The co-primary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17) analysed by the Clopper-Pearson method. Local and systemic reactions and adverse events were recorded. The study is registered at ClinicalTrials.gov, number NCT00808028. 539 participants were enrolled and 511 received all three study vaccinations--116 in the placebo group, 21 in the 60 μg group, 191 in the 120 μg group, and 183 in the 200 μg group. The proportion of participants responding with an hSBA titre equal to or greater than the lower limit of quantitation of the hSBA assays (reciprcocal titres of 7 to 18, depending on test strain) was similar for the two largest doses and ranged from 75·6 to 100·0% for the 120 μg dose and 67·9 to

New recombinant vaccines for the prevention of meningococcal B disease

Directory of Open Access Journals (Sweden)

Taha MK

2012-06-01

Full Text Available Muhamed-Kheir Taha, Ala-Eddine DeghmaneInstitut Pasteur, Unit of Invasive Bacterial Infections and National Reference Center for Meningococci, Paris, FranceAbstract: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis that occurs as epidemic or sporadic cases. The causative agent, Neisseria meningitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no “universal” vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococcus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero®; Novartis, under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and therefore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the

Effect of Co-60 irradiation on hyperimmune antimeningococcus globulins-gamma

International Nuclear Information System (INIS)

Galguera, M.; Le Riverand, E.; Padron, S.

1990-01-01

Globulins-gamma from voluntary blood donors immunized with the Cuban BC antimeningococcus vaccine is now being used in our country for the treatment of the meningococcus disease. This study of the effect of Co-60 irradiation on antimeningococcus globulins-gamma was carried out to try to eliminate the inconvenience shown by the traditionally used sterilization procedures (losses in the filter and persistence of viral contamination). globulins-gamma was obtained by ethanol fractionation and was irradiated at a different dose in solution with different stabilizers and it was also lyophilized. Results of the chemical controls carried out lead to the conclusion that it is possible to use radiosterilization on this product in a lyophilized form. The preservation of bactericidal activity, even after the highest irradiation doses, confirms the above mentioned. 13 refs

Vaccine-Preventable Admissions to an Irish Paediatric Intensive Care

LENUS (Irish Health Repository)

Doyle, Y

2017-05-01

In the Republic of Ireland, the schedule of state-funded immunisation for children is comprehensive and includes diphtheria, pertussis, tetanus, pneumococcus, hepatitis B, meningococcus C, haemophilus B, polio, measles, rubella and mumps. Varicella and meningococcal B vaccines are commercially available but are not currently funded by the government. Each of the illnesses preventable by these vaccines can cause substantial morbidity, and rarely mortality, in infants and children. Our PICU continues to see serious illness due to avoidable infection. There were 39 admissions in a 4 year period, with 34 children surviving to discharge. Nine children were infected with pneumococcus, with 4 deaths. There was one case of pertussis, causing death. Most infections occurred in previously healthy children. These preventable conditions represent a significant burden on children, families, and on social and healthcare resources

[Epidemiology of the meningococcal disease in Catalonia before and after vaccination against serogroup C].

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Martínez, Ana I; Domínguez, Angela; Oviedo, Manuel; Minguell, Sofía; Jansà, Josep M; Codina, Gemma; Vázquez, Julio A

2009-01-01

Meningococcal disease remains a serious public health problem worldwide. In Catalonia, after implementing the vaccination program, there has been a significant decrease in cases caused by meningococcus C. Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine in Catalonia. In case-fatality-rate increased only in serogroup B (3% and 7.4%). Serosubtype P1.15was the most frequent in serogroup B (31%), mainly associated with serotype 4 (80%), and in serogroup C subtype P1.5 (36%), with serotype 2a (86%). During 2008, 5 apparently unrelated cases of B:2a:P1.5 were identified in the same geographic area, with a case-fatality-rate of 80%. Exhaustive surveillance of circulating meningococcal strains is essential.

In silico analysis of different generation β lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

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Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

2014-12-01

Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for β-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of β-lactam antibiotics and concluded that the third generation of β-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis.

A randomized trial of the effect of centralized reminder/recall on immunizations and preventive care visits for adolescents.

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Szilagyi, Peter G; Albertin, Christina; Humiston, Sharon G; Rand, Cynthia M; Schaffer, Stanley; Brill, Howard; Stankaitis, Joseph; Yoo, Byung-Kwang; Blumkin, Aaron; Stokley, Shannon

2013-01-01

To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11-17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P immunizations and preventive visits, with modest costs and modest impact. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

A cross-reacting material CRM197 conjugate vaccine induces diphtheria toxin neutralizing antibody response in children and adolescents infected or not with HIV.

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Silva, Giselle P; Santos, Rafaela S; Pereira-Manfro, Wânia F; Ferreira, Bianca; Barreto, Daniella M; Frota, Ana Cristina C; Hofer, Cristina B; Milagres, Lucimar G

2017-07-05

Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM 197 ) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0.01IU/ml of antibody) and only 8 (19%) showed complete protection (≥0.1IU/ml). About half of the HC (56%) had complete protection before immunization and 6 subjects (12%) had no protection against diphtheria. After one and two vaccine injections, 96% of HC and 64% of HI vaccinees, respectively, showed full protection against diphtheria. These data indicate that CRM 197 was able to induce primary and/or booster response in both groups of individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis.

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Kuttel, Michelle M; Timol, Zaheer; Ravenscroft, Neil

2017-06-29

The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees. Copyright © 2017 Elsevier Ltd. All rights reserved.

Asymtomatic carriage of Neisseria meningitidis and Neisseria lactamica in relation to Streptococcus pneumoniae and Haemophilus influenzae colonization in healthy children: Apropos of 1400 children sampled

International Nuclear Information System (INIS)

Bakir, Mustafa; Yagci, Aysegul; Ulger, Nurver; Akbenlioglu, Cengiz; Ilki, Arzu; Soyletir, Guner

2001-01-01

Meningococcal disease is one of the most important causes of morbidity and mortality among children in many parts of the world. Main reservoir of carriage and site of meningococcal dissemination appears to be the upper respiratory tract. Colonization of Neisseria meningitidis and lactamica and factors affecting this carriage were determined in a group of healthy children aged 0-10 years. Meningococcus and N. lactamica carriage were detected in 17 (1.23%) and 245 (17.7%) of 1382 subjects, respectively. Number (%) of serogroups for meningococci was 1 (6), 5 (29), 0 (0), 1 (6), 1 (6), and 9 (53) for A, B, C, D, W135, and Y, respectively. Having more than three household members, elementary school attendance, pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae were associated with carriage of meningococci, whereas age less than 24-month was associated with carriage of N. lactamica. There was a reverse carriage rate between N. meningitidis and N. lactamica by age which may suggest a possible protective role of N. lactamica against meningococcal colonization among pre-school children

Comparison between nasopharyngeal swab and nasal wash, using culture and PCR, in the detection of potential respiratory pathogens

Directory of Open Access Journals (Sweden)

El Batrawy Sherouk

2011-04-01

Full Text Available Abstract Background Nasopharyngeal carriage of potential pathogens is important as it is both the major source of transmission and the prerequisite of invasive disease. New methods for detecting carriage could improve comfort, accuracy and laboratory utility. The aims of this study were to compare the sensitivities of a nasopharyngeal swab (NPS and a nasal wash (NW in detecting potential respiratory pathogens in healthy adults using microbiological culture and PCR. Results Healthy volunteers attended for nasal washing and brushing of the posterior nasopharynx. Conventional and real-time PCR were used to detect pneumococcus and meningococcus. Statistical differences between the two nasal sampling methods were determined using a nonparametric Mann-Whitney U test; differences between culture and PCR methods were determined using the McNemar test. Nasal washing was more comfortable for volunteers than swabbing (n = 24. In detection by culture, the NW was significantly more likely to detect pathogens than the NPS (p Conclusions Nasal washing and PCR may provide effective alternatives to nasopharyngeal swabbing and classical microbiology, respectively.

Menjugate (Chiron).

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Jones, D H

2001-01-01

Chiron has developed and launched Menjugate, a vaccine for the treatment for meningococcus C infections caused by the pathogen Neisseria meningitidis [177064]. In August 1999, Chiron filed with the UK MCA for a license to market Menjugate. The licence was granted in March 2000 [339082], [344773], [357897] and as of April 2000, a vaccination program was underway in the UK [362152]. Menjugate is indicated for children of 12 months and older, but Chiron was expecting approval in the US for infants younger than 12 months by the end of 2000. The company will also pursue mutual recognition in Europe [376204]. In August 2000, Chiron received marketing clearance for Menjugate from the Irish Medicines Board as a conjugate against meningococcal C disease [378353]. The vaccine employs CRM-conjugate technology, whereby a diphtheria toxoid is used as a carrier protein for the meningitis C-specific antigens. The vaccine is being developed for its potential to provide protection against meningitis in both adults and infants. In July 2000, Chiron entered into a comarketing and co-promotion agreement with Aventis Pasteur under which Aventis will assist Chiron in marketing and sales efforts for Menjugate in the UK [374760].

Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease.

Science.gov (United States)

Jacobsson, Susanne; Hedberg, Sara Thulin; Mölling, Paula; Unemo, Magnus; Comanducci, Maurizio; Rappuoli, Rino; Olcén, Per

2009-03-04

During the recent years, projects are in progress for designing broad-range non-capsular-based meningococcal vaccines, covering also serogroup B isolates. We have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB), in terms of gene prevalence and sequence variations. These data were combined with the results from a similar study, examining the two additional antigens included in the 5CVMB (fHbp and GNA2132). nadA and fHbp v. 1 were present in 38% (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and gna2091 were present in all the Neisseria meningitidis isolates tested (n=95). The level of amino acid conservation was relatively high in GNA1030 (93%), GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the amino acids conserved) appeared to be the most diversified antigen. Consequently, the theoretical coverage of the 5CVMB antigens and the feasibility to use these in a broad-range meningococcal vaccine is appealing.

[Surveillance of Neisseria meningitidis in Argentina, 1993-2005: distribution of serogroups, serotypes and serosubtypes isolated from invasive disease].

Science.gov (United States)

Chiávetta, L; Chávez, E; Ruzic, A; Mollerach, M; Regueira, M

2007-01-01

Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66%) whereas in the period from 1995-2001, serogroup C prevailed (65%). However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco.

Rheumatic disorders in Sub-saharan Africa.

Science.gov (United States)

McGill, P E; Oyoo, G O

2002-04-01

To review prevalence of rheumatic disorders in Sub-saharan Africa and in the context of current medical practice in the region assess the need for service and educational provision. Medline, (English, French). Pre-Medline literature review from the 1950's (Current contents). Various conference reports including attendance at all three AFLAR (African League Against Rheumatism) congresses in the 1990's. Author's personal database. All cited references read in full. The evidence shows rheumatoid arthritis and systemic lupus erythematosus to be increasing in frequency in the indigenous populations of East, Central and South Africa but remaining rare in West Africans. Gout is now more prevalent than ever throughout the subcontinent. HIV has spawned a variety of previously rare spondyloarthropathies (reactive arthritis, psoriatic arthritis, enthesopathy) and changed the epidemiology of pyomyositis and osteomyelitis. Osteoarthritis is a universal problem. Juvenile chronic arthritis is not rare and rheumatic fever is common. Acute and chronic locomotor problems associated with diverse entities such as leprosy, brucellosis, meningococcus, alpha viruses, parasites, fluorosis, rickets and haemoglobinopathies enhance diagnostic diversity and therapeutic and educational requirements. Suggestions made to address the challenge posed by the burden of rheumatic disorders.

Comparison between nasopharyngeal swab and nasal wash, using culture and PCR, in the detection of potential respiratory pathogens.

Science.gov (United States)

Gritzfeld, Jenna F; Roberts, Paul; Roche, Lorna; El Batrawy, Sherouk; Gordon, Stephen B

2011-04-13

Nasopharyngeal carriage of potential pathogens is important as it is both the major source of transmission and the prerequisite of invasive disease. New methods for detecting carriage could improve comfort, accuracy and laboratory utility. The aims of this study were to compare the sensitivities of a nasopharyngeal swab (NPS) and a nasal wash (NW) in detecting potential respiratory pathogens in healthy adults using microbiological culture and PCR. Healthy volunteers attended for nasal washing and brushing of the posterior nasopharynx. Conventional and real-time PCR were used to detect pneumococcus and meningococcus. Statistical differences between the two nasal sampling methods were determined using a nonparametric Mann-Whitney U test; differences between culture and PCR methods were determined using the McNemar test.Nasal washing was more comfortable for volunteers than swabbing (n = 24). In detection by culture, the NW was significantly more likely to detect pathogens than the NPS (p < 0.00001). Overall, there was a low carriage rate of pathogens in this sample; no significant difference was seen in the detection of bacteria between culture and PCR methods. Nasal washing and PCR may provide effective alternatives to nasopharyngeal swabbing and classical microbiology, respectively.

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

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R. Gasparini

2015-01-01

Full Text Available In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics. Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains.

An OMV Vaccine Derived from a Capsular Group B Meningococcus with Constitutive FetA Expression: Preclinical Evaluation of Immunogenicity and Toxicity.

Directory of Open Access Journals (Sweden)

Gunnstein Norheim

Full Text Available Following the introduction of effective protein-polysaccharide conjugate vaccines against capsular group C meningococcal disease in Europe, meningococci of capsular group B remain a major cause of death and can result in debilitating sequelae. The outer membrane proteins PorA and FetA have previously been shown to induce bactericidal antibodies in humans. Despite considerable antigenic variation among PorA and FetA OMPs in meningococci, systematic molecular epidemiological studies revealed this variation is highly structured so that a limited repertoire of antigenic types is congruent with the hyperinvasive meningococcal lineages that have caused most of the meningococcal disease in Europe in recent decades. Here we describe the development of a prototype vaccine against capsular group B meningococcal infection based on a N. meningitidis isolate genetically engineered to have constitutive expression of the outer membrane protein FetA. Deoxycholate outer membrane vesicles (dOMVs extracted from cells cultivated in modified Frantz medium contained 21.8% PorA protein, 7.7% FetA protein and 0.03 μg LPS per μg protein (3%. The antibody response to the vaccine was tested in three mouse strains and the toxicological profile of the vaccine was tested in New Zealand white rabbits. Administration of the vaccine, MenPF-1, when given by intramuscular injection on 4 occasions over a 9 week period, was well tolerated in rabbits up to 50 μg/dose, with no evidence of systemic toxicity. These data indicated that the MenPF-1 vaccine had a toxicological profile suitable for testing in a phase I clinical trial.

CHEMICAL VERSUS SERUM TREATMENT OF EPIDEMIC MENINGITIS.

Science.gov (United States)

Flexner, S; Amoss, H L

1916-05-01

of meningococci, and neither possesses antitoxic power. The mixture of antiserum with lysol and with protargol reduces to a certain extent the antileukotactic and antiphagocytic effect of the chemicals; but this action is insufficient to set aside wholly the injurious effects which they produce. It follows, therefore, that whatever theoretical advantages might accrue from a bactericidal activity exerted by these chemicals independently of the type of meningococcus causing epidemic meningitis, is more than offset by the harmful effects which they cause. Hence specific antiserum seems to provide the logical therapeutic agent with which to combat epidemic meningitis, since it is itself innocuous and promotes those processes essential to recovery from the disease. The problem up to the present has been that of producing an antiserum which represents the several types of the meningococcus, and this problem is now in a fair way to being solved.

Commentary: Impact of meningococcal group B OMV vaccines, beyond their brief.

Science.gov (United States)

Petousis-Harris, Helen

2017-10-19

Meningococcal group B outer membrane vesicle vaccines have been used widely in Cuba, New Zealand, and Brazil. They are immunogenic and initially assessed largely by their ability to induce serum bactericidal activity. Measures of efficacy indicate good protection against homologous strains in older children and adults. Effectiveness appears broader than predicted by immunogenicity and efficacy studies. The recent discovery that meningococcal group B OMVs may protect against the related Neisseria species N.gonorrhoeae suggests more to these interesting antigen collections than meets the eye. Currently there are two OMV-containing group B vaccines available, the new recombinant protein-based Bexsero® developed by Novartis and VA-MENGOC-BC® developed by the Finlay institute in Cuba. Also, a third group B vaccine based on two recombinant factor H binding proteins (Trumenba®, Pfizer), has recently been licenced but it does not include OMV. This commentary explores the population impact that group B OMV vaccines have had on meningococcal and gonorrhoea diseases. Given the heterologous effect against diverse strains of the meningococcus observed in older children and adults, and recent evidence to suggest moderate protection against gonorrhoea, there may be a role for these vaccines in programmes targeting adolescents and groups high at risk for both meningococcal disease and gonorrhoea.

Medical complications following splenectomy.

Science.gov (United States)

Buzelé, R; Barbier, L; Sauvanet, A; Fantin, B

2016-08-01

Splenectomy is attended by medical complications, principally infectious and thromboembolic; the frequency of complications varies with the conditions that led to splenectomy (hematologic splenectomy, trauma, presence of portal hypertension). Most infectious complications are caused by encapsulated bacteria (Meningococcus, Pneumococcus, Hemophilus). These occur mainly in children and somewhat less commonly in adults within the first two years following splenectomy. Post-splenectomy infections are potentially severe with overwhelming post-splenectomy infection (OPSI) and this justifies preventive measures (prophylactic antibiotics, appropriate immunizations, patient education) and demands prompt antibiotic management with third-generation cephalosporins for any post-splenectomy fever. Thromboembolic complications can involve both the caval system (deep-vein thrombophlebitis, pulmonary embolism) and the portal system. Portal vein thrombosis occurs more commonly in patients with myeloproliferative disease and cirrhosis. No thromboembolic prophylaxis is recommended apart from perioperative low molecular weight heparin. However, some authors choose to prescribe a short course of anti-platelet medication if the post-splenectomy patient develops significant thrombocytosis. Thrombosis of the portal or caval venous system requires prolonged warfarin anticoagulation for 3 to 6 months. Finally, some studies have suggested an increase in the long-term incidence of cancer in splenectomized patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Emergence and control of epidemic meningococcal meningitis in sub-Saharan Africa.

Science.gov (United States)

Mohammed, Idris; Iliyasu, Garba; Habib, Abdulrazaq Garba

2017-02-01

For more than a century, meningitis epidemics have regularly recurred across sub-Saharan Africa, involving 19 contiguous countries that constitute a 'meningitis belt' where historically the causative agent has been serogroup A meningococcus. Attempts to control epidemic meningococcal meningitis in Africa by vaccination with meningococcal polysaccharide (PS) vaccines have not been successful. This is largely because PS vaccines are poorly immunogenic in young children, do not induce immunological memory, and have little or no effect on the pharyngeal carriage. Meningococcal PS-protein conjugate vaccines overcome these deficiencies. Conjugate meningococcal vaccine against serotype A (MenAfriVac) was developed between 2001 and 2009 and deployed in 2010. So far, 262 million individuals have been immunized across the meningitis belt. The public health benefits of MenAfriVac have already been demonstrated by a sharp decline in reported cases of meningococcal disease in the countries where it has been introduced. However, serogroup replacement following mass meningitis vaccination has been noted, and in 2015 an epidemic with a novel strain of serogroup C was recorded in Niger and Nigeria for the first time since 1975. This has posed a serious challenge toward elimination of meningococcal meningitis epidemics in the African. For an effective control of meningococcal meningitis in the African meningitis belt, there is a need for an effective surveillance system, provision of rapid antigen detection kits as well as affordable vaccine that provides protection against the main serogroups causing meningitis in the sub-region.

Care of the college student.

Science.gov (United States)

Unwin, Brian K; Goodie, Jeffrey; Reamy, Brian V; Quinlan, Jeffrey

2013-11-01

There are approximately 20 million students in U.S. colleges and universities. Although this population is characterized as having good health, 600,000 students report some form of disability or some type of medical problem, including attention-deficit/hyperactivity disorder, learning disabilities, psychiatric disorders, and chronic illnesses, among others. Physicians can enhance youth transition to an adult model of health care; the use of self-care skills checklists is one recommended method to assist with the transition. Stimulant medications are effective for treating adults with attention-deficit/hyperactivity disorder, but physicians should use caution when prescribing stimulants to college students because of the high rates of medication diversion in this population. Depression, anxiety, posttraumatic stress disorder, sleep problems, and eating disorders are common in college students and can significantly impact performance. Emphasis on immunization of students for influenza, meningococcus, and pertussis is necessary because of the low rates of compliance. Screening and interventions for obesity, tobacco use, and substance abuse are important because of the high prevalence of these problems in college students. Screening for alcohol abuse facilitates identification of students with problem drinking behaviors. Students who are war veterans should be monitored for suicidal ideation and posttraumatic stress disorder. Lesbian, gay, bisexual, transgender, and questioning students are at risk of harassment and discrimination. Caution should be exercised when prescribing medications to college athletes to avoid violation of National Collegiate Athletic Association eligibility rules.

Acute polyarthritis in a young patient caused by meningococcal and parvovirus B19 infections: a case report and review of the literature.

Science.gov (United States)

Lavoipierre, Virginie; Dellyes, Anna; Aubry, Camille; Zandotti, Christine; Lafforgue, Pierre; Parola, Philippe; Lagier, Jean-Christophe

2016-12-20

Meningococcal infection is a multifaceted disease including acute polyarthritis. This presentation should be known by clinicians in order to prevent delay in treatment. We report what we believe to be the first case of an association of parvovirus B19 and meningococcal polyarthritis in a young adult. A 19-year-old Caucasian woman presented to our hospital with fever, intense leg pain, and a transient rash. A physical examination showed asymmetric polyarthritis and no neurological abnormalities. A parvovirus B19 polymerase chain reaction performed using a blood sample and knee fluid aspirate came back positive, but serology was negative for immunoglobulin M and positive for immunoglobulin G. A blood culture was positive for serotype C meningococcus; a polymerase chain reaction performed for Neisseria meningitidis was positive in joint fluid but negative in blood samples (performed after antibiotic treatment had begun). Our patient was treated with ceftriaxone for 15 days, associated with analgesic therapy. Hydroxychloroquine treatment was introduced 5 months after the onset of polyarthritis because of persisting inflammatory arthralgia. To the best of our knowledge, this is the first case report of polyarthritis caused by concomitant meningococcal and parvovirus B19 infections. This unusual presentation of meningococcal disease may have resulted from the persistent parvovirus B19 infection. Our experience with this case illustrates the need for a systematic approach to the diagnosis of febrile acute polyarthritis. Only long-term follow-up will reveal if this infectious polyarthritis will evolve towards an autoimmune rheumatism.

Patterns of complications of neonatal and infant meningitis on MRI by organism: A 10 year review

International Nuclear Information System (INIS)

Jaremko, Jacob L.; Moon, Anna S.; Kumbla, Surekha

2011-01-01

Introduction: Imaging of meningitis in neonates and infants is not routine, but is frequent for complications. Aside from tuberculosis and herpesvirus, imaging findings related to most responsible pathogens are thought to be nonspecific, but few studies exist. We reviewed the imaging features of complicated meningitis in infants and neonates at our hospital in the past decade, hypothesizing that patterns of complications might be more specific than previously recognized. Methods: 10 yr retrospective review of magnetic resonance imaging (MRI) and microbiology data for all neonates (age <30 d) and infants (age <1 yr) imaged for possible complications of meningitis at a tertiary children's hospital. Results: We had 63 patients (25 neonates, 38 infants). The 3 most common pathogens were streptococcal species (n = 32, mean age 4.7 mo), E. coli (n = 9, mean 1.2 mo), and herpes simplex virus (n = 4). The most common findings were meningeal enhancement (78% of those given IV contrast), infarct (52%), subdural collection (35%), and ventriculomegaly (32%). E. coli presented much more frequently with ventriculomegaly (64% vs. 22%) than streptococcal species. Extensive infarcts were typical of streptococcal meningitis (13/32, 41%) and rarely seen with other organisms (2/31, 6%, p = 0.001). All 3 cases of Serratia meningitis had large parenchymal abscesses, and 2/4 cases of meningococcus had occipital cortical necrosis. Conclusion: Although overlap was present, each organism responsible for neonatal/infant meningitis produced an identifiable pattern of complications on MRI. Recognising these patterns can help the radiologist suggest possible diagnosis and influence early management.

Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

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Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

2012-06-01

Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.

A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation From Immunogenicity

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David J. Dowling

2016-12-01

Full Text Available Background. Group B Neisseria meningitidis, an endotoxin-producing gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs or soluble lipopolysaccharide (LPS represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific in vitro culture systems.Methods. OMVs from wild type and inactivated lpxL1 gene mutant N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and PGE2 production, as well as cell surface activation markers (HLA-DR, CD86, CCR7. OMV immunogenicity was assessed in mice.Results. ΔlpxLI native OMVs demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, Bacillus Calmette–Guérin (BCG tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI native OMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.Conclusions. A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.

[Implementation of meningococcal B vaccination (Bexsero®) in France: Physicians' perceptions and experiences of a few months after marketing approval].

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Levy, C; Bechet, S; Cohen, R

2016-01-01

In December 2013, the French public health authorities recommended the use of Bexsero® (meningococcus B vaccine) in areas with endemic risk and for patients at risk for invasive meningococcal B disease. In this context, InfoVac-France performed a national survey a few months after the implementation of the vaccine to evaluate physicians' perceptions and experiences with this new vaccine. This survey was proposed by email in April 2014 to the InfoVac network. An initial email explained the purpose of this study and proposed an online questionnaire. Between April 29 and May 16, 2014, 1502 physicians answered online: 502 GPs (33%), 939 pediatricians (63%), and 61 other specialists (4%). In response, 91% of physicians would like to use this vaccine and 87% of pediatricians versus 50% of GPs knew that the vaccine was marketed. Physicians had been informed of the vaccine mostly via the InfoVac network (61%). The immunization schedules for all ages were slightly known by physicians (9% for GPs and 43% of pediatricians). This vaccination was still rarely proposed (18%) more often because it was not reimbursed to patients (62%). Although 39% of physicians were planning to propose the vaccine to their patients, 54% remained undecided. A total of 9% of pediatricians and 2% of GPs had already used this vaccination. This InfoVac-France survey shows that physicians would support the implementation of this vaccine, but questions persist as to its effectiveness, impact on carriage, and duration of protection. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as 'virulence genes'

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Saunders Nigel J

2006-05-01

Full Text Available Abstract Background Neisseria meningitidis causes the life-threatening diseases meningococcal meningitis and meningococcal septicemia. Neisseria gonorrhoeae is closely related to the meningococcus, but is the cause of the very different infection, gonorrhea. A number of genes have been implicated in the virulence of these related yet distinct pathogens, but the genes that define and differentiate the species and their behaviours have not been established. Further, a related species, Neisseria lactamica is not associated with either type of infection in normally healthy people, and lives as a harmless commensal. We have determined which of the genes so far identified in the genome sequences of the pathogens are also present in this non-pathogenic related species. Results Thirteen unrelated strains of N. lactamica were investigated using comparative genome hybridization to the pan-Neisseria microarray-v2, which contains 2845 unique gene probes. The presence of 127 'virulence genes' was specifically addressed; of these 85 are present in N. lactamica. Of the remaining 42 'virulence genes' only 11 are present in all four of the sequenced pathogenic Neisseria. Conclusion Assessment of the complete dataset revealed that the vast majority of genes present in the pathogens are also present in N. lactamica. Of the 1,473 probes to genes shared by all four pathogenic genome sequences, 1,373 hybridize to N. lactamica. These shared genes cannot include genes that are necessary and sufficient for the virulence of the pathogens, since N. lactamica does not share this behaviour. This provides an essential context for the interpretation of gene complement studies of the pathogens.

Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes.

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Pajon, Rolando; Yero, Daniel; Niebla, Olivia; Climent, Yanet; Sardiñas, Gretel; García, Darién; Perera, Yasser; Llanes, Alejandro; Delgado, Maité; Cobas, Karem; Caballero, Evelin; Taylor, Stephen; Brookes, Charlotte; Gorringe, Andrew

2009-12-11

The difficulty of inducing an effective immune response against the Neisseria meningitidis serogroup B capsular polysaccharide has lead to the search for vaccines for this serogroup based on outer membrane proteins. The availability of the first meningococcal genome (MC58 strain) allowed the expansion of high-throughput methods to explore the protein profile displayed by N. meningitidis. By combining a pan-genome analysis with an extensive experimental validation to identify new potential vaccine candidates, genes coding for antigens likely to be exposed on the surface of the meningococcus were selected after a multistep comparative analysis of entire Neisseria genomes. Eleven novel putative ORF annotations were reported for serogroup B strain MC58. Furthermore, a total of 20 new predicted potential pan-neisserial vaccine candidates were produced as recombinant proteins and evaluated using immunological assays. Potential vaccine candidate coding genes were PCR-amplified from a panel of representative strains and their variability analyzed using maximum likelihood approaches for detecting positive selection. Finally, five proteins all capable of inducing a functional antibody response vs N. meningitidis strain CU385 were identified as new attractive vaccine candidates: NMB0606 a potential YajC orthologue, NMB0928 the neisserial NlpB (BamC), NMB0873 a LolB orthologue, NMB1163 a protein belonging to a curli-like assembly machinery, and NMB0938 (a neisserial specific antigen) with evidence of positive selection appreciated for NMB0928. The new set of vaccine candidates and the novel proposed functions will open a new wave of research in the search for the elusive neisserial vaccine.

Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants.

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Beth Holder

2010-11-01

Full Text Available Epstein-Barr virus (EBV and cytomegalovirus (CMV are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.

Streptococcus pneumoniae aislados de infecciones invasivas: serotipos y resistencia antimicrobiana Streptococcus pneumoniae isolated from invasive infections: serotypes and antimicrobial resistance

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Gladys Antonia Cueto Montoya

2007-03-01

Full Text Available Las meningoencefalitis bacterianas constituyen una enfermedad invasiva importante, quizás no tanto por su frecuencia, como por la gravedad de su cuadro. Los cambios en la epidemiología de los síndromes neurológicos infecciosos en Cuba a partir de la vacunación contra meningococo BC y Haemophilus influenzae b han hecho que el Streptococcus pneumoniae constituya el agente causal más frecuente. Debido al incremento de la resistencia de este microorganismo a los antibióticos habituales, se realizaron modificaciones al régimen terapéutico convencional, fundamentalmente en las meningitis pediátricas. Es necesario lograr el aislamiento en cultivo de este agente para conocer los serotipos más frecuentes en el país, y lograr una vacuna neumocócica conjugada, así como para la vigilancia de las cepas frente a los antimicrobianos.The bacterial meningoencephalitis is an important invasive disease, not only because of its frequency, but also because of the severity of its picture. The changes in the epidemiology of the neurological infectious syndromes in Cuba starting from the vaccination against meningococcus BC and Haemophilus infuenzae b have made that Streptococcus pneumoniae be the most frequent causal agent. Due to the increase of the resistance of this microorganism to habitual antibiotics, modifications were made in the conventional therapeutic regimen, mainly in the pediatric meningitis. It is necessary to achieve the isolation in culture of this agent to know the most common serotypes in the country, to attain a conjugated pneumococcal vaccine, and to keep the surveillance of the strains against the antimicrobials.

A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA.

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Keiser, Paul B; Gibbs, Barnett T; Coster, Trinka S; Moran, E Ellen; Stoddard, Mark B; Labrie, Joseph E; Schmiel, Deborah H; Pinto, Valerian; Chen, Ping; Zollinger, Wendell D

2010-10-08

This phase 1 clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from a lpxL2(-) synX(-) mutant of strain 44/76 with opcA expression stabilized. Thirty-four volunteers were assigned to one of the three dose groups (25 mcg, 25 mcg with aluminum hydroxide adjuvant, and 50 mcg) to receive three intramuscular injections at 0, 6 and 24 weeks. Specific local and systemic adverse events (AEs) were solicited by diary and at visits on days 1, 2, 7 and 14 after each vaccination and at the end of the study at 30 weeks. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again two days later. Blood for antibody measurements and bactericidal assays were drawn 0, 14, and 42 days after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in serum bactericidal activity (SBA) to the wild-type parent of the vaccine strain with high opcA expression at 6 weeks after the third dose was 12/26 (0.46, 95% confidence interval 0.27-0.65). Antibody levels to OpcA were significantly higher in vaccine responders than in non-responders (p=0.008), and there was a trend for higher antibody levels to the lipooligosaccharide (LOS) (p=0.059). Bactericidal depletion assays on sera from volunteers with high-titer responses also indicate a major contribution of anti-OpcA and anti-LOS antibodies to the bactericidal response.These results suggest that genetically modified NOMV vaccines can induce protection against group B meningococcus. Copyright © 2010 Elsevier Ltd. All rights reserved.

Getting it right from birth to kindergarten: what's new in the Rourke Baby Record?

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Rourke, Leslie; Leduc, Denis; Constantin, Evelyn; Carsley, Sarah; Rourke, James; Li, Patricia

2013-04-01

To provide an overview of the 2011 edition of the Rourke Baby Record (RBR), which includes developments on its website and new related initiatives that incorporate recent literature on preventive health care for children aged 0 to 5 years. As in past RBR editions, recommendations are identified as supported by good, fair, or consensus evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care in 2011. New information and recommendations are given for growth monitoring, nutrition, physical examination maneuvers, and immunizations for varicella, pneumococcus, meningococcus, and rotavirus. There is now good evidence for converting to the World Health Organization growth charts adapted for Canada, universal newborn hearing screening, and use of immunization pain reduction strategies. Anticipatory guidance has been updated for safe sleeping, health supervision of foster children, fetal alcohol spectrum disorder, lead and anemia screening risk factors, and dental care and oral health. New RBR website items include a parent resources section, modifications for unique populations such as those living in Nunavut, a version of the RBR that highlights what has changed from the 2009 version for quick viewing, and an expansion of the "Explore the RBR" feature with associated links to relevant information. A one-visit-per-page format is now available. The 2011 RBR is endorsed by the College of Family Physicians of Canada and the Canadian Paediatric Society, and is available in English and French in national and Ontario versions. The 2011 RBR is an updated, evidence-based, practical knowledge translation tool for preventive health care for infants from birth to age 5 years that includes extensive Web-based resources for health care professionals, students, residents, and parents.

Meningitis and Climate: From Science to Practice

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Perez Garcia-Pando, Carlos; Thomson, Madeleine C.; Stanton, Michelle C.; Diggle, Peter J.; Hopson, Thomas; Pandya, Rajul; Miller, Ron L.; Hugonnet, Stephane

2014-01-01

Meningococcal meningitis is a climate sensitive infectious disease. The regional extent of the Meningitis Belt in Africa, where the majority of epidemics occur, was originally defined by Lapeysonnie in the 1960s. A combination of climatic and environmental conditions and biological and social factors have been associated to the spatial and temporal patterns of epidemics observed since the disease first emerged in West Africa over a century ago. However, there is still a lack of knowledge and data that would allow disentangling the relative effects of the diverse risk factors upon epidemics. The Meningitis Environmental Risk Information Technologies Initiative (MERIT), a collaborative research-to-practice consortium, seeks to inform national and regional prevention and control strategies across the African Meningitis Belt through the provision of new data and tools that better determine risk factors. In particular MERIT seeks to consolidate a body of knowledge that provides evidence of the contribution of climatic and environmental factors to seasonal and year-to-year variations in meningococcal meningitis incidence at both district and national scales. Here we review recent research and practice seeking to provide useful information for the epidemic response strategy of National Ministries of Health in the Meningitis Belt of Africa. In particular the research and derived tools described in this paper have focused at "getting science into policy and practice" by engaging with practitioner communities under the umbrella of MERIT to ensure the relevance of their work to operational decision-making. We limit our focus to that of reactive vaccination for meningococcal meningitis. Important but external to our discussion is the development and implementation of the new conjugate vaccine, which specifically targets meningococcus A

Encefalomielite disseminada aguda e vacinação antimeningocócica A e C: relato de caso Acute disseminated encephalomyelitis: association with meningococcal A and C vaccine: case report

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Marco O. Py

1997-09-01

Full Text Available Os autores descrevem o caso clínico de paciente do sexo feminino, de 25 anos, que desenvolveu encefalomielite aguda disseminada (EDA iniciando-se cinco dias após vacinação para meningococcus A e C (Pasteur-Meríeux na campanha de vacinação realizada em dezembro de 1995 na cidade do Rio de Janeiro. Houve excelente resposta clínica e neurorradiológica após tratamento com corticosteróides em altas doses (pulsoterapia. Não foram encontrados relatos sobre a associação entre a vacina antimeningocócica e a EDA. A associação entre EDA e leptospirose ou infecções por Mycoplasma sugerem porém que a síndrome pode ser precipitada não só por viroses ou vacinação antiviral como também pela exposição do organismo a proteínas e polissacarídeos de bactérias.A 25-year-old woman developed acute disseminated post-vaccinal encephalomyelitis (ADEM following vaccination with A plus C meningococcal vaccine (Pasteur-Merieux. Fast disappearance of symptoms and gradual resolution of MR1 demyelinating lesions occurred after steroid treatment with high doses of intravenous methylprednisolone. To our knowledge, ADEM has not been previously described in association with meningococcal vaccine. Although most cases of ADEM occur following viral infections and vaccination, the syndrome has previously been related to leptospirosis and Mycoplasma pneumoniae infections. This suggests that it may also be related to exposure to polysaccharide-protein vaccines such as the Group A plus Group C meningococcal vaccine.

Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

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White Brian

2010-11-01

Full Text Available Abstract Background The genus Neisseria contains two important yet very different pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic species, of which N. lactamica is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally. Results Non-pathogenic N. lactamica exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal cps region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent. Conclusion The three Neisseria species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.

Characterization of Vaccination Policies for Attendance and Employment at Day/Summer Camps in New York State.

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Prescott, William A; Violanti, Kelsey C; Fusco, Nicholas M

2018-01-01

New York state requires day/summer camps to keep immunization records for all enrolled campers and strongly recommends requiring vaccination for all campers and staff. The objective of this study was to characterize immunization requirements/recommendations for children/adolescents enrolled in and staff employed at day/summer camps in New York state. An electronic hyperlink to a 9-question survey instrument was distributed via e-mail to 178 day/summer camps located in New York state cities with a population size greater than 100 000 people. A follow-up telephone survey was offered to nonresponders. The survey instrument included questions pertaining to vaccination documentation policies for campers/staff and the specific vaccines that the camp required/recommended. Fisher's exact and Chi-square tests were used to analyze categorical data. Sixty-five day/summer camps responded to the survey (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a policy/procedure for documenting vaccinations for campers and staff, respectively. Camps that had a policy/procedure for campers were more likely to have a policy/procedure for staff ( P = .0007). Age-appropriate vaccinations that were required/recommended for campers by at least 80% of camps included: measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B, inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and varicella. Age-appropriate vaccinations that were required/recommended for staff by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR, meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap). Vaccination policies at day/summer camps in New York state appear to be suboptimal. Educational outreach may encourage camps to strengthen their immunization policies, which may reduce the transmission of vaccine-preventable diseases.

Vaccination coverage in systemic lupus erythematosus-a cross-sectional analysis of the German long-term study (LuLa cohort).

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Chehab, Gamal; Richter, Jutta G; Brinks, Ralph; Fischer-Betz, Rebecca; Winkler-Rohlfing, Borgi; Schneider, Matthias

2018-05-10

Vaccinations are an important measure to prevent infections in immunocompromised patients. The knowledge of vaccination coverage and reasons for non-vaccination in patients with SLE is scarce. The aim of this study was to assess coverage rates of selected vaccinations in a representative sample of SLE patients and to identify predictors for non-vaccination. In 2013, information on selected vaccinations (coverage, application and reservations) and on demographics, clinical parameters and health beliefs was assessed by means of a self-reported questionnaire among a representative sample of SLE patients in Germany (LuLa cohort). Five hundred and seventy-nine patients participated. Vaccination status was primarily checked by their general practitioner (57.3%). Of all the patients, 24.9% did not get their vaccination status checked at all, 16.1% had generally been advised against the use of vaccinations by a physician, and 37.5% stated that they had rejected vaccinations themselves. Their main reasons were fears of developing a lupus flare (21.8%) or adverse events (13.5%). A greater belief by patients in the doctor controlling one's health and the general benefit of medication prevented the rejection of vaccines. Vaccination coverage was low for all recorded vaccinations (tetanus 65.8%, influenza 45.2%, pneumococcus 32.2% and meningococcus 6.1%). Older age was predictive of receiving influenza and pneumococcal vaccination. The same applies for CSs >7.5 mg for receiving influenza vaccination. Vaccination coverage in SLE patients is poor and reflects insufficient implementation of national and international recommendations. Rheumatologists need to recognize patients' reservations against vaccinations, to communicate their importance and safety and to give individual recommendations to patients and their health-care providers. German Clinical Trials Register, www.germanctr.de, DRKS00011052.

Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

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Schininà Maria

2010-09-01

Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

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Giuntini, Serena; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Meningococcal Carriage in Military Recruits and University Students during the Pre MenB Vaccination Era in Greece (2014-2015).

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Tryfinopoulou, Kyriaki; Kesanopoulos, Konstantinos; Xirogianni, Athanasia; Marmaras, Nektarios; Papandreou, Anastasia; Papaevangelou, Vassiliki; Tsolia, Maria; Jasir, Aftab; Tzanakaki, Georgina

2016-01-01

The aim of the study was to estimate the meningococcal carriage rate and to identify the genotypic characteristics of the strains isolated from healthy military recruits and university students in order to provide data that might increase our understanding on the epidemiology of meningococcus and obtain information which helps to evaluate the potential effects on control programs such as vaccination. A total of 1420 oropharyngeal single swab samples were collected from military recruits and university students on voluntary basis, aged 18-26 years. New York City Medium was used for culture and the suspected N. meningitidis colonies were identified by Gram stain, oxidase and rapid carbohydrate utilization tests. Further characterisation was carried out by molecular methods (multiplex PCR, MLST, WGS). The overall carriage rate was of 12.7%; 15% and 10.4% for recruits and university students respectively. MenB (39.4%) was the most prevalent followed by MenY (12.8%) and MenW (4.4%). Among the initial 76 Non Groupable (NG) isolates, Whole Genome Sequence Analysis (WGS) revealed that 8.3% belonged to MenE, 3.3% to MenX and 1.1% to MenZ, while, 53 strains (29.4%) were finally identified as capsule null. Genetic diversity was found among the MenB isolates, with 41/44 cc and 35 cc predominating. Meningococcal carriage rate in both groups was lower compared to our previous studies (25% and 18% respectively) with predominance of MenB isolates. These findings, help to further our understanding on the epidemiology of meningococcal disease in Greece. Although the prevalence of carriage seems to have declined compared to our earlier studies, the predominant MenB clonal complexes (including 41/44cc and 35cc) are associated with invasive meningococcal disease.

Adapting immunisation schedules for children undergoing chemotherapy.

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Fernández-Prada, María; Rodríguez-Martínez, María; García-García, Rebeca; García-Corte, María Dolores; Martínez-Ortega, Carmen

2018-02-01

Children undergoing chemotherapy for cancer have special vaccination needs after completion of the treatment. The aim of this study was to evaluate the adaptation of post-chemotherapy vaccination schedules. An observational study was performed on a retrospective cohort that included all children aged from 0 to 14 years, who completed chemotherapy in a tertiary hospital between 2009 and 2015. Inclusion and exclusion criteria were applied. Immunisation was administered in accordance with the guidelines of the Vaccine Advisory Committee of the Spanish Association of Paediatrics. Primary Care immunisation and clinical records of the Preventive Medicine and Public Health Department were reviewed. Of the 99 children who had received chemotherapy, 51 (70.6% males) were included in the study. As regards the type of tumour, 54.9% had a solid organ tumour, and 45.1% had a haematological tumour. Post-chemotherapy immunisation was administered to 70.6%. The most common vaccines received were: diphtheria-tetanus-pertussis or diphtheria-tetanus (54.9%), meningococcus C (41.2%), and seasonal influenza (39.2%). The rate of adaptation of the immunisation schedule after chemotherapy was 9.8%. The pneumococcal conjugate vaccine against 7v or 13v was administered to 21.6% of study subjects. However, only 17.6% received polysaccharide 23v. None received vaccination against hepatitis A. No statistically significant differences were observed between adherence to immunisation schedules and type of tumour (P=.066), gender (P=.304), or age (P=.342). Post-chemotherapy immunisation of children with cancer is poor. The participation of health professionals in training programs and referral of paediatric cancer patients to Vaccine Units could improve the rate of schedule adaptation and proper immunisation of this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Optic neuritis in paediatric patients: Experience over 27 years and a management protocol.

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Monge Galindo, L; Martínez de Morentín, A L; Pueyo Royo, V; García Iñiguez, J P; Sánchez Marco, S; López-Pisón, J; Peña-Segura, J L

2018-03-08

In this article, we present our experience on optic neuritis (ON) and provide a diagnostic/therapeutic protocol, intended to rule out other aetiologies (particularly infection), and a fact sheet for parents. We conducted a descriptive, retrospective study of patients with ON over a 27-year period (1990-2017). A review of the available scientific evidence was performed in order to draft the protocol and fact sheet. Our neuropaediatrics department has assessed 20,744 patients in the last 27 years, of whom 14 were diagnosed with ON: 8 had isolated ON, 1 had multiple sclerosis (MS), 1 had clinically isolated syndrome (CIS), 3 had acute disseminated encephalomyelitis, and 1 had isolated ON and a history of acute disseminated encephalomyelitis one year previously. Patients' age range was 4-13 years; 50% were boys. Eight patients were aged over 10: 7 had isolated ON and 1 had MS. Nine patients had bilateral ON, and 3 had retrobulbar ON. MRI results were normal in 7 patients and showed involvement of the optic nerve only in 2 patients and optic nerve involvement + central nervous system demyelination in 5. Thirteen patients received corticosteroids. One patient had been vaccinated against meningococcus-C the previous month. Progression was favourable, except in the patient with MS. A management protocol and fact sheet are provided. ON usually has a favourable clinical course. In children aged older than 10 years with risk factors for MS or optic neuromyelitis (hyperintensity on brain MRI, oligoclonal bands, anti-NMO antibody positivity, ON recurrence), the initiation of immunomodulatory treatment should be agreed with the neurology department. The protocol is useful for diagnostic decision-making, follow-up, and treatment of this rare disease with potentially major repercussions. The use of protocols and fact sheets is important. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18.

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Stephen D Bentley

2007-02-01

impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.

Vaccination coverage among social and healthcare workers in ten countries of Samu-social international sites.

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Marshall, Esaie; Salmon, Dominique; Bousfiha, Nadia; Togola, Yacouba; Ouedraogo, François; Santantonio, Maud; Dieng, Coumba Khadidja; Tartière, Suzanne; Emmanuelli, Xavier

2017-09-18

We aim to determine the vaccination coverage of social and healthcare workers in International sites of Samusocial, providing emergency care to homeless people, and to assess factors associated with having received necessary doses at adulthood. Data on immunization coverage of social and healthcare workers were provided by a cross-sectional survey, conducted from February to April 2015 among 252 Samusocial workers in 10 countries. Vaccination status and characteristics of participants were collected through a self-administered questionnaire. Prevalence rate ratio (PRR) of vaccination status was calculated using Poisson regression models. Among 252 Samusocial social and health workers who felt a questionnaire, median age was 39years, 42.1% were female, 88.9% were in contact with homeless beneficiaries (19.1% health workers). Overall, 90.1% of Samusocial staff felt adult vaccinations was useful and 70.2% wished to receive booster doses in future. Vaccination coverage at adulthood was satisfactory for diphtheria and poliomyelitis (96%), but low for influenza (20.8%), meningococcus (50.5%), hepatitis B (56.3%), yellow fever (58.1%), measles (81.3%) and pertussis (90.7%). The main reasons for not having received vaccination booster doses were forgetting the dates of booster doses (38.4%) and not having received the information (13.5%). In adjusted analysis, prevalence of up-to-date for vaccination schedule was 35% higher among health workers than among social workers (aPRR=1.35, 95%CI: 1.01-1.82, P=0.05) and was 56% higher among workers who had a documentary evidence of vaccination than in those who did not (aPRR=1.56, 95%CI: 1.19-2.02, P=0.001). The Samusocial International workers vaccine coverage at adulthood was insufficient and disparate by region. It is necessary to strengthen the outreach of this staff and increase immunization policy for hepatitis B, diphtheria, tetanus, and measles, as well as for yellow fever, rabies and meningococcal ACYW135 vaccines in at

SENSITIVITAS KUMAN NEISSERIA MENINGITIDIS YANG DIISOLASI DARI JAMAAH HAJI INDONESIA TERHADAP BEBERAPA ANTIBIOTIK

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Muljati Prijanto

2012-09-01

Full Text Available The meningitis meningococcal disease caused by Neisseriae meningitidis is an infection of meninges and cerebrospinal fluid (CSF of the brain and the spinal cord. N. meningitidis is classified into 13 serogroups based on the immunologic reactivity of the capsular polysaccharide. Since 1993 the number of cases and carriers of haj pilgrims from Indonesia have increased. In 1996 the carrier rate was 9,4%, and case fatality rate of Indonesian haj pilgrims in Saudi Arabia was 71,4%. The dominant serogroup was serogroup B. The meningitis vaccine of serogroup B is not available yet. Until now there is not enough information of the laboratory results from the hospital in Saudi Arabia, regarding the strain that caused the infection of haj pilgrims from Indonesia. To prevent transmission of the disease among Haj pilgrims, since 1997, chemoprophylaxis with ciprofloxacine has been given to close contact persons of haj pilgrim patient. The objectives of this study are: First, to know the effectiveness of ciprofloxacin in decreasing the carrier rate of meningitis meningococcus in haj pilgrims. Second, to identify the serogroup of N. meningitidis isolated from carrier or patient and thirdly to know the sensitivity of bacteria to several antibiotics recommended by WHO. Nasofaringeal swabs were taken from 914 haj pilgrims from group of contact person of cases or suspected cases and 311 haj pilgrims from control group at embarkation in Jakarta. Ciprofloxacin was given to the study group in Saudi Arabia. Isolation and serogrouping were carried out for serogroup A, B, C. The result shows that the effectiveness of ciprofloxacin to N. meningitidis in the treated group were 98.58% and control were 85.54%, respectively. The serogroup of N. meningitidis is isolated from 13 carriers of treated group 69,23% could not be classified as serogroup A, B, or C. In the control group, 45 isolated strains from carriers consist of serogroup B 40%, serogroup C 28,9%, serogroup A 20

Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

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Santolaya, María Elena; O'Ryan, Miguel L; Valenzuela, María Teresa; Prado, Valeria; Vergara, Rodrigo; Muñoz, Alma; Toneatto, Daniela; Graña, Gabriela; Wang, Huajun; Clemens, Ralf; Dull, Peter M

2012-02-18

meningococcus B variants circulating worldwide will be determined by national surveys. Novartis Vaccines and Diagnostics. Copyright © 2012 Elsevier Ltd. All rights reserved.

The impact of new technologies on vaccines.

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Talwar, G P; Diwan, M; Razvi, F; Malhotra, R

1999-01-01

Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these

Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

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Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; Fermon, F; Page, A-L; Djingarey, M H; Hugonnet, S; Harrison, O B; Rebbetts, L S; Tekletsion, Y; Watkins, E R; Hill, D; Caugant, D A; Chandramohan, D; Hassan-King, M; Manigart, O; Nascimento, M; Woukeu, A; Trotter, C; Stuart, J M; Maiden, McJ; Greenwood, B M

2014-01-04

A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (pvaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). PSA-TT was highly

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

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Ostergaard, Lars; Vesikari, Timo; Absalon, Judith; Beeslaar, Johannes; Ward, Brian J; Senders, Shelly; Eiden, Joseph J; Jansen, Kathrin U; Anderson, Annaliesa S; York, Laura J; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert; Radley, David; Maansson, Roger; Prégaldien, Jean-Louis; Ginis, John; Staerke, Nina B; Perez, John L

2017-12-14

MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus. We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months. Immunogenicity was assessed in serum bactericidal assays that included human complement (hSBAs). We used 14 meningococcal B test strains that expressed vaccine-heterologous factor H-binding proteins representative of meningococcal B epidemiologic diversity; an hSBA titer of at least 1:4 is the accepted correlate of protection. The five primary end points were the proportion of participants who had an increase in their hSBA titer for each of 4 primary strains by a factor of 4 or more and the proportion of those who had an hSBA titer at least as high as the lower limit of quantitation (1:8 or 1:16) for all 4 strains combined after dose 3. We also assessed the hSBA responses to the primary strains after dose 2; hSBA responses to the 10 additional strains after doses 2 and 3 were assessed in a subgroup of participants only. Safety was assessed in participants who received at least one dose. In the modified intention-to-treat population, the percentage of adolescents who had an increase in the hSBA titer by a factor of 4 or more against each primary strain ranged from 56.0 to 85.3% after dose 2 and from 78.8 to 90.2% after dose 3; the percentages of young adults ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively. Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively. Responses to the 4 primary strains were predictive of responses to the 10 additional strains. Most of those who received Men

Rapport sur la Meningite Cerebrospinale Epidemique a Teheran

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A. Machhoun

1958-01-01

Full Text Available Thirty cases have been studied in the recent epidemic of meningococcal meningitis. In fourteen of these cases organisms were isolated."nIn all these the organisms were proved to be meningococcus type A; with following characteristics:"n1-Different culture media were tried; blood agar was found to be the best.                                                                                                                                                             2-One week after the onset of the illness, serum test was tried with the patient's sera and meningococci type A. All were positive (1/160-1/640. The reaction was negative with the organisms of types B, C and also with the sera of patients suffering from lymphocytic meningitis.                              3-Crossed agglutination was positive with the serum obtained from each patient; and the organisms isolated from the other; thus"nprov ing the common origin of the epidemic. 4-In most of the cases seroprecipitation from centrifugated C.S.F. with antimeningococcal A serum was positive. 5-All the strains obtained were highly sensitive to sulphonamides, The sensitivity to penicillin, erythromycin, oleandomycin and chloramphenicol was fairly good; but to other antibiotics it was less marked. 6-This sensitivity to sulfonamides has not deterioted up to this date, and we have not found any strain resistent to this drug. 7-The clinical pattern of the disease has somewhat changed during the course of the epidemic. At first classical types were more often seen, hut later the cases admitted were more severe, with Coma and convulsion

Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

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L. Chiavetta

2007-03-01

studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco.

Calendário vacinal na infância e adolescência: avaliando diferentes propostas Vaccination schedule for childhood and adolescence: comparing recommendations

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Ricardo Becker Feijó

2006-07-01

covering the period from 2000 to 2005. SUMMARY OF THE FINDINGS: Local epidemiological and socioeconomic factors and the available infrastructure often define the priorities of immunobiological recommendations. The publications reviewed, both national and international, differ in terms of the vaccination schedule for tuberculosis, poliomyelitis, rotavirus, pertussis, pneumococcus, meningococcus, varicella and hepatitis A. In Brazil, there are Special Immunobiology Referral Centers (CRIE - Centros de Referência de Imunobiológicos Especiais, which, according to specific criteria, offer the population immunobiologicals that are unavailable on the public health network. CONCLUSIONS: While the use of a universal schedule is impossible due to epidemiological and operational differences, there are similarities that can be incorporated with different populations, as long as technical and scientific criteria are respected.

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

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Chang Hsiu-Li

2006-02-01

Full Text Available Abstract Background Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. Methods Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs. Results Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the

Etiology of bacterial meningitis among children aged 2-59 months in Salvador, Northeast Brazil, before and after routine use of Haemophilus influenzae type b vaccine Etiologia da meningite bacteriana em crianças com idade entre 2 e 59 meses em Salvador, Nordeste do Brasil, antes e depois do uso rotineiro da vacina para Haemophilus influenzae tipo b

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Cristiana M. Nascimento-Carvalho

2004-06-01

Full Text Available OBJECTIVE: To describe the frequency of etiologic agents of bacterial meningitis (BM among children aged 2-59 months in a sample of patients in Salvador, Northeast Brazil, with emphasis on the frequency of BM of unknown etiology (BMUE, just before, during and after the implementation of routine immunization of infants with Haemophilus influenzae type b (Hib vaccination. METHOD: Demographic, clinical and cerebrospinal fluid (CSF information was collected from the chart of every patient, aged 2-59 months, whose CSF exam was performed at the CSF Lab - José Silveira Foundation, between January 1989 and December 2001. Every CSF exam was completely performed according to standard methods. The etiologic diagnosis was based on either culture and/or latex-agglutination test. When the agent was only seen on Gram stained smear, the diagnosis was descriptive. BMUE was defined as: glucose 100 mg / dl, white blood cell count > 20 cells / mm³, percentage of neutrophils > 80%. RESULTS: Of 1519 patients, 894 (58.9% had normal exams and BM was diagnosed in 95 (6.2%. Etiologic agents were: Hib (44.2%, meningococcus (13.7%, Gram-negative bacilli (11.6%, Mycobacterium tuberculosis (6.3%, pneumococcus (4.2%, other agents (4.2%; BMUE was diagnosed in 15.8% of cases with BM. By analysing the frequency of BMUE and Hib among all exams performed yearly, the peaks were recorded in 1989 (5.3% and 1990 (16.9%, respectively, decreasing to 0.7% and 0% in 2001. CONCLUSION: It is possible that the implementation of the conjugate Hib vaccine during the 1990's has been decreasing not only the occurrence of Hib meningitis but also of BMUE.OBJETIVO: Descrever a freqüência dos agentes etiológicos de meningite bacteriana (MB em amostra das crianças com idade entre 2 e 59 meses, em Salvador, Nordeste do Brasil, com ênfase na freqüência de MB de etiologia indeterminada (MBEI, antes, durante e após a implementação da imunização rotineira de lactentes com vacina para

Os níveis de saúde na região da Grande São Paulo Health levels in the area of the "Greater São Paulo" (Brasil

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João Yunes

1970-12-01

(proportional deaths ratio tended to a normal form of a "J", which demonstrated a regular health level of the studied are. According to the main causes of death, health levels showed an inadequate condition, for, although Circulatory Diseases and Neoplasm are the two main causes of death, even in developed countries, next comes Childhood Diseases, Respiratory Diseases, Digestive System Diseases and Infection and Parasitoses Diseases like in underdeceloped ares. The area of the Greater São Paulo (Brazil itself in an intermediate position between developed and underdeveloped countries according to the causes of death that occurs in its area. Tuberculoses, Measles, Siphilis, Tetanus, Dysenteria, Whooping Cough and Diphteria were among the communicable diseases the main causes of death. The infantil mortality rate since 1961 (61.34/1000 had increased rapidly and had reached 74.92/1000 live birth in 1967. This increase was caused either by neo-natal or post-neonatal mortality. The trends happened to the city and to the State of S. Paulo, showing in this way an agravation in the health levels. Such event is unvailable with the characteristics of the area of the Greater S. Paulo (Brazil, since this is the most urbanized and social-economical developed region, not only of the State of S. Paulo, but also of Brazil, and may be of Latin America. Among the main causes of death in the infant mortality rate, appears in decreasing order, prenatal, natal and neonatal deaths, Digestive system Diseases, Respiratory Diseases and Infection Diseases. Among the main Communicable Diseases in the infant mortality period appears Measles, Whooping Cough, Tetanus, Tuberculoses, Dysenteria, Meningococcus Infections, Smallpox and Encephalites. Among the main predisponent factors, were pointed out poor maternal and infant care, lack of maternity beds to indigent people, high proportion of home deliveries, lack of qualified persons to attend infant care, inadequate enviromental health (40% of population