Sample records for meningococcus

  1. Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine. (United States)

    Lai, Zengzu; Schreiber, John R


    Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.

  2. Meningococcus Disease Photos (United States)

    ... BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ... Immunization Action Coalition (IAC), a non-profit organization, works to ... facilitates communication about the safety, efficacy, and use of vaccines ...

  3. Complement-Mediated Bactericidal Activity of Anti-Factor H Binding Protein Monoclonal Antibodies against the Meningococcus Relies upon Blocking Factor H Binding ▿ (United States)

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


    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity. PMID:21708990

  4. Meningitis - meningococcal (United States)

    Meningococcal meningitis; Gram negative - meningococcus ... Meningococcal meningitis is caused by the bacteria Neisseria meningitidis (also known as meningococcus). Meningococcus is the most common cause ...

  5. MF59 oil-in-water emulsion in combination with a synthetic TLR4 agonist (E6020) is a potent adjuvant for a combination Meningococcus vaccine. (United States)

    Singh, Manmohan; Kazzaz, Jina; Ugozzoli, Mildred; Baudner, Barbara; Pizza, Mariagrazia; Giuliani, Marzia; Hawkins, Lynn D; Otten, Gillis; O'Hagan, Derek T


    The inclusion of a potent TLR4 immune potentiator to a recombinant antigen vaccine formulation enhances both the magnitude and the breadth of the engendered immune response. One such immune potentiator (TLR4 agonist E6020) was evaluated with recombinant Men B antigens delivered in MF59 sub-micron adjuvant emulsion. The ability of this formulation to enhance serum antibody and bactercidal titers was investigated. The co-delivery of E6020 within MF59 enhanced both the serum and bactericidal titers for Men B antigens and for Men B antigens combined with Men ACWY-CRM conjugate vaccine. The delivery of TLR4 agonist within MF59 emulsion oil droplets leads to a more potent response in comparison to the TLR4 when admixed with MF59 emulsion.

  6. 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


    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.

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

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    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.

  8. Meningococcal disease in the Netherlands. Background information for the Health Council

    NARCIS (Netherlands)

    Knol MJ; de Melker HE; Berbers GAM; Ravenhorst MB; Ruijs WLM; van Vliet JA; Kemmeren JM; Suijkerbuijk A; van Lier EA; Sanders EAM; van der Ende A; RVP; I&V


    Meningococcal disease is a very serious infectious disease caused by a bacterium, the meningococcus. There are different types of meningococcus; people become ill mainly from the B, C, W and Y serogroups. Since 2002, vaccination against serogroup C meningococcal disease has been included in the

  9. Prospects for eradication of meningococcal disease


    Nadel, Simon


    Meningococcal meningitis and septicaemia remain a serious global health threat. This review focuses on the epidemiology of meningococcal disease following the recent implementation of effective vaccines and the potential utility of a vaccine against serogroup B meningococcus.

  10. Bacterial meningitis in the era of paediatric vaccination against the ...

    African Journals Online (AJOL)

    Hib), Streptococcus pneumoniae (the pneumococcus), and Neisseria meningitidis (the meningococcus) are still the most common bacteria causing acute meningitis in infants and children worldwide, despite the availability of effective vaccines.

  11. Indirect effects by meningococcal vaccines: herd protection versus herd immunity. (United States)

    Bröker, Michael


    The term "herd immunity" for the indirect effect of meningococcal conjugate vaccines is inaccurate. A more appropriate term is "herd protection," because this term correctly describes the public effects imparted by vaccination campaigns against the meningococcus.

  12. Riboregulation in Neisseria meningitidis

    NARCIS (Netherlands)

    Huis in 't Veld, R.A.G.


    Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions that differ in nutrient supply such as the nasopharynx, blood and cerebrospinal fluid by changing

  13. Burden of invasive bacterial disease among children younger than 5 ...

    African Journals Online (AJOL)

    Background: Haemophilus influenzae b (Hib), pneumococcus and meningococcus are responsible for high mortality and morbidity in children younger than 5 years of age worldwide. Hib containing vaccine was introduced in July 2008 in Togo; and baseline data are available on bacterial meningitis prior to PCV13 vaccine ...

  14. Effects of Long-Term Immunization with Multiple Antigens. (United States)


    the discovery of experimental allergic encephalomyelitis (as it is known today). Monkeys, guinea pigs , and rabbits develop an accelerated form of dis...seminated encephalomyelitis after injection of brain or spinal-cord homogenates combined with the immunologic adjuvant. 4 5 Experimental allergic...Hemophilus influenzae and meningococcus polysaccharides. Lancet 1:190-192, 1979. * 45. Paterson, P. Y. Experimental autoimmune (allergic) encephalo

  15. TLR-mediated NF-kB-dependent cytokine production is differently affected by HIV therapeutics

    DEFF Research Database (Denmark)

    Melchjorsen, Jesper; Paludan, Søren Riis; Mogensen, Trine

      Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumonia and N. Meningococcus. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary...

  16. Emerging clinical experience with vaccines against group B meningococcal disease. (United States)

    Wilkins, A L; Snape, M D


    The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus (MenB). Both of these vaccines are based on sub-capsular proteins of the meningococcus, an approach that overcomes the challenges set by the poorly immunogenic MenB polysaccharide capsule but adds complexity to predicting and measuring the impact of their use. This review describes the development and use of MenB vaccines to date, from the use of outer membrane vesicle (OMV) vaccines in MenB outbreaks around the world, to emerging evidence on the effectiveness of the newly available vaccines. While recent data from the United Kingdom supports the potential for protein-based vaccines to provide direct protection against MenB disease in immunised children, further research is required to understand the breadth and duration of this protection. A more detailed understanding of the impact of immunisation with these vaccines on nasopharyngeal carriage of the meningococcus is also required, to inform both their potential to induce herd immunity and to preferentially select for carriage of strains not susceptible to vaccine-induced antibodies. Although a full understanding of the potential impact of these vaccines will only be possible with this additional information, the availability of new tools to prevent the devastating effect of invasive MenB disease is a significant breakthrough in the fight against childhood sepsis and meningitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Immunogenicity of meningococcal B polysaccharide conjugated to tetanus toxoid or CRM197 via adipic acid dihydrazide. (United States)

    Bartoloni, A; Norelli, F; Ceccarini, C; Rappuoli, R; Costantino, P


    Vaccine development against Group B Neisseria meningitidis is complicated by the nature of the capsular polysaccharide, which is alpha 2-8-linked poly-sialic acid, identical in structure to the poly-sialic acid found in many mammalian tissues during development. To test the feasibility of a vaccine based on this polysaccharide, we synthesized several conjugates of meningococcal B polysaccharide linked to a carrier protein (tetanus toxoid or diphtheria CRM197), via an adipic acid dihydrazide (ADH) spacer. All conjugates induced a strong immune response. However, most of the antibodies were not directed against the Meningococcus B polysaccharide and could not be inhibited by the purified polysaccharide alone. Further investigations showed that the antibodies recognized an epitope composed by the junction between the spacer and the polysaccharide and protein, that is not present in the native polysaccharide and is generated during the coupling reaction. This epitope becomes immunodominant with respect to the poorly immunogenic polysaccharide. While the majority of the immune response is directed against the above epitope, the conjugates induced also an immune response against the Meningococcus B polysaccharide. The anti-Meningococcus B antibodies elicited are of the IgM and IgG class and are inhibitable by the polysaccharide. Moreover, they are bactericidal, thus suggesting that they would induce protection against disease.

  18. Temperature triggers immune evasion by Neisseria meningitidis. (United States)

    Loh, Edmund; Kugelberg, Elisabeth; Tracy, Alexander; Zhang, Qian; Gollan, Bridget; Ewles, Helen; Chalmers, Ronald; Pelicic, Vladimir; Tang, Christoph M


    Neisseria meningitidis has several strategies to evade complement-mediated killing, and these contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an increase in ambient temperature. We have identified three independent RNA thermosensors located in the 5' untranslated regions of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing. Therefore increased temperature (which occurs during inflammation) acts as a 'danger signal' for the meningococcus, enhancing its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors. Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium.

  19. Clinical and epidemiological aspects of generalized meningococcal infections in children and adolescents of Saint-Petersburg

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    Yu. V. Lobzin


    Full Text Available Generalized meningococcal infection belongs to the group of diseases with a high risk of initiation of life-threatening conditions and death outcomes. There was carried out a retrospective analysis of clinical and epidemiological features of generalized meningococcal infections in children and adolescents of Saint Petersburg in 1995–2014 on the basis of the analysis of 884 medical records of the patients hospitalized at Scientific Research Institute of Children’s Infections. With general prevalence of the children of the first years of life among the patients, there has been revealed the tendency to reduction in the portion of children of the first year of life from 41,4% in 1995 to 22,2% by 2014, and the increase in the number of patients of 1–3 years old from 19,3–30,5% in 1995–1996 to 46,4–46,4% in 2013–2014. Among the number of etiologically identified cases (59,4% the majority of them has been caused by serogroup B meningococcus (58,5%, in 24,2% – by serogroup C meningococcus, in 11,2% – by serogroup A meningococcus, and in 6,1% – by rare (W135/Y and unspecified strains N.meningitidis. Within the recent years there has been identified the tendency of rate growth concerning the diseases caused by serogroup C meningococci, remarkable for a severe course and high rate of death cases. Total death indicator for the investigated period has averaged 4,2%, with the variability from 0 to 12,5% for different years.

  20. [New vaccines against group B meningococcal diseases]. (United States)

    Hietalahti, Jukka; Meri, Seppo


    There has been no efficient general vaccine against serogroup B meningococcus (MenB), since its polysialic acid capsule is of low immunogenicity and could potentially induce autoimmunity. Reverse vaccinology has revealed new promising protein candidates for vaccine development. One of them is factor H-binding protein (fHbp), which has the potential to curb the alternative pathway of human complement. As fHbp can elicit antibodies that promote complement-mediated lysis, a vaccine partly based on it has been introduced against MenB infections. FHbp has been the milestone protein for structural vaccinology to create optimal chimeric antigens for vaccine use.

  1. Cutaneous Involvement in Acute Meningococcemia (Study of an Epidemic in Delhi

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    V Ramesh


    Full Text Available Thirty (88.2% out of 34 children with skin lesions were observed during the recent epidemic of meningococcus group A infection in Delhi. Purpuric lesions were the commonest (60%, maculo-papular in 26-67% and faint pink macules′m 13.33% Conjunctivae were affected m 3. These eruptions appeared within 6 hours: ulcers and gangrene appeared after 7 days in one child. Severe vascular damage was seen on histoplthology of the ulcers as compared to the early lesions. Gangrene of the extremities developed during the recovery phase when all other signs of the disease had subsided.

  2. El papel del médico de la familia en el control de los síndromes neurológicos infecciosos

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    Ibrahin Quintana Jardines


    Full Text Available En el presente trabajo se exponen las actividades que debe desarrollar el Médico y Enfermera de la Familia en el control de los Síndromes Neurológicos Infecciosos, destacándose, que en estos momentos en que se ha sobrepasado el período epidémico que provocó el meningococo en los últimos años, es necesario el abordaje de estas enfermedades fundamentalmente a través de las inmunizaciones contra el Haemophilus influenzae tipo b y el meningococo, el reforzamiento de las actividades de control de foco y la participación en las actividades de rehabilitación y evitación de las secuelas que estas entidades provocan.This paper presents the activities to be carried out by the family physician and nurse in order to control Infectious Neurological Syndromes, underlining that at these moments, when the epidemic period provoked by the meningococcus in the last years has been overcome, it is necessary to FACE these diseases mainly throug immunizations against Haemophilus influenzae type B and meningococcus, to reinforce those activities for focus control and to participate in activities for the rehabilitation and the prevention of the sequelae produced by these inities.

  3. Immunology Update: New Vaccines. (United States)

    Starr, S Paul


    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  4. The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis? (United States)

    Maiden, Martin C J


    The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.

  5. Influence of antibiotic therapy prior to admission on the efficacy of classical methods for the diagnosis of meningococcal disease. (United States)

    Nemescu, Roxana Elena; Iancu, Luminiţa Smaranda; Dorneanu, Olivia Simona; Ursu, Ramona Gabriela; Dorobăţ, Carmen Mihaela


    To assess the influence of preadmission antibiotic therapy on the results of the classical methods for bacteriological confirmation of meningococcal disease (MD). Retrospective study of the MD cases diagnosed in the "St. Parascheva" Universitary Clinical Infectious Diseases Iaşi between 1994 and 2011. The etiological diagnosis was made by identifying the meningococcus in the CSF (cerebrospinal fluid) in 71.9% of the 323 patients and by blood culture in 8%. Preadmission antibiotic therapy received 39% of the patients, thus the sensitivity of test was significantly reduced: direct examination from 64.6% to 43.2% (p antibiotic therapy significantly increased the ratio of cases in which meningococcus was not detected in CSF by any of the classical methods (44% compared to 17.9% in the cases without prior treatment). The proportion of cases in which meningococcal isolation was done by two methods decreased from 38.5% to 19.2%, and of those by all three methods from 16.9% to 5.6% (p antibiotic therapy also decreased the rate of positive blood cultures from 14.7% to 3.5% (Fisher's exact test, p = 0.009). Antibiotic treatment prior to admission significantly decreases the percentage of patients with MD in which meningococcal isolation can be done; this requires the use of a more sensitive diagnosis method (ex. qPCR).

  6. Cuantificación de IGG contra los componentes inmunogénicos de VA-ENGOC-BC en plasma de lactantes vacunados

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    José Rodríguez Canosa


    Full Text Available Debido a las características particulares de la respuesta inmune en lactantes, así como a la eficacia mostrada por la vacuna cubana antimeningocóccica VA-MENGOC-BC, nos propusimos cuantificar la respuesta de la inmunoglobulina G contra los componentes inmunogénicos de los meningococos B y C presentes en la vacuna, en lactantes vacunados. Se tomó muestra por punción capilar a 109 lactantes entre 3 y 6 meses de edad antes de la vacunación a los 31,4 ± 2 días después de la primera y 32,3 ± días después de la segunda dosis vacunal. Se determinaron las concentraciones de inmunoglobulina G contra cada inmunógeno de la vacuna. Los niveles de inmunoglobulina G específica prevacunación, fueron elevadas contra el meningococo C. Se produjo un incremento estadísticamente significativo de anticuerpos para ambos inmunógenos después de la primera y segunda dosis, más marcado contra el meningococo C en la primera y para el meningococo B en la segunda, lo que apoya la presencia de memoria inmunológicaDue to the particular characteristics of the immune response in infants and to the efficacy shown by the Cuban antimeningococcal vaccine denominated VA-MENGOC-BC, we propose ourselves to quantify the response of immunoglobulin G against the immunogenic components of the meningococci B and C present in the vaccine among the vaccinated infants. The sample was taken by capillary puncture from 109 infants between 3 and 6 months before vaccination, at 31.4±2 days after the first dose and at 32.3± days after the second one. The concentrations of immunoglobulin G against each immunogen of the vaccine were determined. The levels of prevaccination specific immunoglobulin G were elevated against meningococcus C. There was a statistically significant increase of atibodies for both immunogens after the first and second dose. It was more marked against meningococcus C in the first, and for meningococcus B in the secons one, which supports the presence of

  7. Reverse Vaccinology: Developing Vaccines in the Era of Genomics (United States)

    Sette, Alessandro; Rappuoli, Rino


    The sequence of microbial genomes made all potential antigens of each pathogen available for vaccine development. This increased by orders of magnitude potential vaccine targets in bacteria, parasites, and large viruses and revealed virtually all their CD4+ and CD8+ T cell epitopes. The genomic information was first used for the development of a vaccine against serogroup B meningococcus, and it is now being used for several other bacterial vaccines. In this review, we will first summarize the impact that genome sequencing has had on vaccine development, and then we will analyze how the genomic information can help further our understanding of immunity to infection or vaccination and lead to the design of better vaccines by diving into the world of T cell immunity. PMID:21029963

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

    International Nuclear Information System (INIS)

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


    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

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

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


    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.

  10. Epidemic meningococcal disease: synthesis of a hypothetical immunoepidemiologic model. (United States)

    Griffiss, J M


    A hypothetical model of the epidermic behavior of Neisseria meningitidis, based upon the induction of susceptibility to disseminated disease by circulating IgA, is presented. The model is based on the assumption that epidemic susceptibility is acquired as a result of induction of serum IgA by cross-reacting enteric bacteria, the priming organism. Co-colonization with the appropriate strain of N. meningitidis then may result in disseminated disease. Colonization by either bacterium in the absence of the other results in reinforcement of the commensal relationship. Slow, silent, fecal-oral transmission of the priming organism determines the time/space characteristics of an epidemic; interruption of fecal-oral transmission aborts it. Aerosol transmission of the meningococcus determines the magnitude of an epidemic. Independent, age-related acquisition of both capsular polysaccharide and lipopolysaccharide antibodies provides immunity in the absence of aberrantly high levels of co-specific serum IgA.

  11. Vaccine-Preventable Admissions to an Irish Paediatric Intensive Care

    LENUS (Irish Health Repository)

    Doyle, Y


    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

  12. Vaccination coverage of adolescents: Results of a Defense and Citizenship Day-based survey. (United States)

    Buscail, C; Gagnière, B


    Vaccination coverage among French young adults is not routinely measured. Every French adolescent aged between 16 and 18years must take part in the Defense and Citizenship Day (French acronym JDC). We aimed to assess vaccination coverage among young adults for hepatitis B, group C meningococcus meningitis, human papillomavirus (HPV), and measles. We also aimed to assess the proportion of adolescents who received the pertussis booster between the age of 11 and 13years. The survey took place from January 19th to 26th, 2015 at the JDC center of Rennes, France. Vaccination coverage data was collected on site from the adolescents' health records. We collected the number of doses received and the dates of administration for each type of vaccine. A properly vaccinated adolescent was defined as having received the right number of doses according to the vaccination schedule. A total of 467 adolescents attended the JDC Day: 408 (87.4%) had brought their health record or an equivalent document. Vaccination coverage was 92.6% [90.1-95.1] for measles, 34.6% [30-39.2] for group C meningococcus meningitis, 40.7% [35.9-45.5] for hepatitis B, and 30.1% [23.9-36.3] of girls had been vaccinated against HPV. Of all adolescents, 60.1% [55.7-64.9] received a dose of the pertussis vaccine between 11 and 13years of age. Our results are similar to those of other data sources. With regard to the difficulty of assessing vaccination coverage in that age group, we believe recruitment bias was minimized due to our study location. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. [Invasive meningococcal disease in Navarra in the era of a meningococcal C vaccine]. (United States)

    Morales, Desirée; Moreno, Laura; Herranz, Mercedes; Bernaola, Enrique; Martínez-Baz, Iván; Castilla, Jesús


    Systematic childhood vaccination against meningococcus C has had a considerable impact on meningococcal invasive disease (MID). The aim of this study is to perform an analysis on the epidemiology, the clinical features, and the factors associated with a worse prognosis of MID, in the era of a meningococcal C vaccine. The study included confirmed cases of MID in children less than 15 years of age in Navarra, Spain, between 2008 and 2014. The risk of death or permanent sequelae was evaluated according to the presence of clinical features and analytical parameters at diagnosis. The average annual incidence was 7.9 cases per 100,000 children, with the highest attack rate in children < 1 year. Of 53 cases analysed, 87% were due to meningococcus B. Fever (100%), rash (91%), and elevation of procalcitonin (94%) were the most frequent findings at diagnosis. Some sign of shock was observed in 70% upon arrival at the hospital. The case-fatality rate was 3.8% and 10 % survived with permanent sequelae. Glasgow coma scale < 15 (odds ratio [OR]= 9.2), seizure (OR=8.3), sepsis without meningitis (OR=9.1), thrombocytopenia (OR=30.5), and disseminated intravascular coagulation (OR= 10.9) showed a greater association with a worse prognosis. The MID continues to be a significant cause of morbidity and mortality in children. Therefore, new advances are needed in the prevention, early diagnosis, and detection of the factors associated with poor prognosis. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. New recombinant vaccines for the prevention of meningococcal B disease

    Directory of Open Access Journals (Sweden)

    Taha MK


    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

  15. Maternal and infant antibody response to meningococcal vaccination in pregnancy. (United States)

    de Andrade Carvalho, A; Giampaglia, C M; Kimura, H; de Pereira, O A; Farhat, C K; Neves, J C; Prandini, R; da Silva Carvalho, E; Zarvos, A M


    The antigenic capacity of a mixed vaccine prepared with polysaccharides of meningococcus groups A and C, the placental transfer of antibodies, and the persistence of positive titres in the infant were evaluated in 21 pregnant women and their offspring during an epidemic of meningitis in São Paulo, Brazil; and antibody response was assessed in 29 infants vaccinated at less than 6 months of age. Antibodies were detected by passive haemagglutination; the high titres found and the high frequency of positive results are thought to be due to the use of a more sensitive technique. Increased antibody titres were found in most women, and there was evidence for passive transfer to the newborn, especially with regard to antibody type C. However, passive transfer was irregular, and the presence of antibodies in the mother did not guarantee their presence in the child. Passive transfer lasted for only 2-5 months. Vaccination in children under 6 months of age had poor results; only 1 child seroconverted.

  16. Emergence and control of epidemic meningococcal meningitis in sub-Saharan Africa. (United States)

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


    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.

  17. Histopathology of vaccine-preventable diseases. (United States)

    Solomon, Isaac H; Milner, Danny A


    The widespread use of vaccines has been one of the most important medical advances in the last century, saving trillions of dollars and millions of lives. Despite local eradication of some infections, travellers returning from affected areas may cause outbreaks through reintroduction of pathogens to individuals who are unable to receive vaccines for medical reasons or who have declined vaccination for non-medical reasons. Infections that would otherwise be uncommonly encountered by anatomical pathologists should therefore remain in the differential diagnosis for immunocompromised and unvaccinated patients. We review here the histopathological features and ancillary testing required for diagnosis of all illnesses preventable by vaccines that are currently approved for use by the United States Food and Drug Administration, organized into three sections: viral infections preventable by routine vaccination (measles, mumps, rubella, varicella, rotavirus, polio, hepatitis A, hepatitis B, influenza, and human papillomavirus), bacterial infections preventable by routine vaccination (diptheria, tetanus, pertussis, Haemophilus influenzae, pneumococcus, and meningococcus), and infections with specific vaccine indications (anthrax, typhoid, tuberculosis, rabies, Japanese encephalitis, yellow fever, smallpox, and adenovirus). Histopathology for the less common diseases is illustrated in this review. Awareness of a patient's immune and/or vaccine status is a crucial component of the infectious disease work-up, especially for rare diseases that may not otherwise be seen. © 2016 John Wiley & Sons Ltd.

  18. [Management of purpura fulminans lesions in children]. (United States)

    Pasquesoone, L; Belkhou, A; Gottrand, L; Guerreschi, P; Duquennoy-Martinot, V


    Purpura fulminans is a pediatric life-threatening emergency with a significant mortality, combining: septic shock, extensive purpuric lesions and disseminated intravascular coagulation. The most frequent bacterial pathogen is the meningococcus. The medical management includes antibiotics, corticoids, vascular filling and catecholamines. Purpura fulminans is characterized by the extent of hemorrhagic and mainly thrombotic lesions, attributed to the alteration in the vascular endothelium functions. Damage of soft tissues combines large necrotic areas and more or less extensive distal ischemic lesions. Necrotic lesions can be deep, reaching skin, subcutaneous tissue, fascia, muscle and sometimes even the bone. The importance of the aesthetic and functional sequelae as well as future quality of life, depend on the quality of surgical management for these wide and deep lesions. Fasciotomy is sometimes urgently needed in the case of a clinical compartment syndrome, confirmed by a high-pressure measurement in the muscle compartments. Debridement of necrotic lesions and amputations are only performed after a clear delineation of necrotic areas, between 10 days and 3 weeks of evolution. If an amputation is necessary, it must focus on the residual bone length, considering the child's growth potential. The coverage of tissue loss uses all the plastic surgery techniques, more or less complex, in order to reduce scars to minimum for these children. Rehabilitation follow-up includes physical and psychological care, which are essential until adulthood. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Commentary: Impact of meningococcal group B OMV vaccines, beyond their brief. (United States)

    Petousis-Harris, Helen


    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.

  20. 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. (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


    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, 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

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

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


    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.

  2. Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information. (United States)

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


    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.

  3. Menjugate (Chiron). (United States)

    Jones, D H


    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].

  4. Vaccination coverage of children with inflammatory bowel disease after an awareness campaign on the risk of infection. (United States)

    Fleurier, Aude; Pelatan, Cecile; Willot, Stephanie; Ginies, Jean-Louis; Breton, Estelle; Bridoux, Laure; Segura, Jean-Francois; Chaillou, Emilie; Jobert, Agathe; Darviot, Estelle; Cagnard, Benoit; Delaperriere, Nadege; Grimal, Isabelle; Carre, Emilie; Wagner, Anne-Claire; Sylvestre, Emmanuelle; Dabadie, Alain


    Children with inflammatory bowel disease are at risk of vaccine-preventable diseases mostly due to immunosuppressive drugs. To evaluate coverage after an awareness campaign informing patients, their parents and general practitioner about the vaccination schedule. Vaccination coverage was firstly evaluated and followed by an awareness campaign on the risk of infection via postal mail. The trial is a case-control study on the same patients before and after the awareness campaign. Overall, 92 children were included. A questionnaire was then completed during a routine appointment to collect data including age at diagnosis, age at data collection, treatment history, and vaccination status. Vaccination rates significantly increased for vaccines against diphtheria-tetanus-poliomyelitis (92% vs. 100%), Haemophilus influenzae (88% vs. 98%), hepatitis B (52% vs. 71%), pneumococcus (36% vs. 57%), and meningococcus C (17% vs. 41%) (pChildren who were older at diagnosis were 1.26 times more likely to be up-to-date with a minimum vaccination schedule (diphtheria-tetanus-poliomyelitis, pertussis, H. influenzae, measles-mumps-rubella, tuberculosis) (p=0.002). Informing inflammatory bowel disease patients, their parents and general practitioner about the vaccination schedule via postal mail is easy, inexpensive, reproducible, and increases vaccination coverage. This method reinforces information on the risk of infection during routine visits. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Care of the college student. (United States)

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


    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.

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

    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


    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.

  7. Medical complications following splenectomy. (United States)

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


    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.

  8. 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


    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

  9. Vaccination coverage of patients with inborn errors of metabolism and the attitudes of their parents towards vaccines. (United States)

    Cerutti, Marta; De Lonlay, Pascale; Menni, Francesca; Parini, Rossella; Principi, Nicola; Esposito, Susanna


    To evaluate vaccination coverage of children and adolescents with inborn errors of metabolism (IEMs) and the attitudes of their parents towards vaccination, the vaccination status of 128 patients with IEM and 128 age- and gender-matched healthy controls was established by consulting the official vaccination chart. In children with IEMs, compared with healthy controls, low vaccination rates and/or delays in administration were observed for pneumococcal conjugate, meningococcus C, measles, mumps, rubella, diphtheria-tetanus-pertussis-inactivated polio, Bacillus Calmette-Guerin, and influenza vaccines. Among the parents of IEM patients, vaccine schedule compliance was primarily driven by the doctors at the hospital's reference centres; among the parents of the healthy controls, compliance was driven by the primary care paediatricians. These results show that IEM patients demonstrate sub-optimal vaccination coverage. Further studies of the different vaccines in each IEM disorder and educational programmes aimed at physicians and parents to increase immunization coverage in these patients are urgently needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Meningitis and Climate: From Science to Practice (United States)

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


    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

  11. Optic neuritis in paediatric patients: Experience over 27 years and a management protocol. (United States)

    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


    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.

  12. A Critical Role for the cccA Gene Product, Cytochrome c2, in Diverting Electrons from Aerobic Respiration to Denitrification in Neisseria gonorrhoeae (United States)

    Hopper, Amanda C.; Li, Ying


    Neisseria gonorrhoeae is a microaerophile that, when oxygen availability is limited, supplements aerobic respiration with a truncated denitrification pathway, nitrite reduction to nitrous oxide. We demonstrate that the cccA gene of Neisseria gonorrhoeae strain F62 (accession number NG0292) is expressed, but the product, cytochrome c2, accumulates to only low levels. Nevertheless, a cccA mutant reduced nitrite at about half the rate of the parent strain. We previously reported that cytochromes c4 and c5 transfer electrons to cytochrome oxidase cbb3 by two independent pathways and that the CcoP subunit of cytochrome oxidase cbb3 transfers electrons to nitrite. We show that mutants defective in either cytochrome c4 or c5 also reduce nitrite more slowly than the parent. By combining mutations in cccA (Δc2), cycA (Δc4), cycB (Δc5), and ccoP (ccoP-C368A), we demonstrate that cytochrome c2 is required for electron transfer from cytochrome c4 via the third heme group of CcoP to the nitrite reductase, AniA, and that cytochrome c5 transfers electrons to nitrite reductase by an independent pathway. We propose that cytochrome c2 forms a complex with cytochrome oxidase. If so, the redox state of cytochrome c2 might regulate electron transfer to nitrite or oxygen. However, our data are more consistent with a mechanism in which cytochrome c2 and the CcoQ subunit of cytochrome oxidase form alternative complexes that preferentially catalyze nitrite and oxygen reduction, respectively. Comparison with the much simpler electron transfer pathway for nitrite reduction in the meningococcus provides fascinating insights into niche adaptation within the pathogenic neisseriae. PMID:23543713

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

    Directory of Open Access Journals (Sweden)

    Marco O. Py


    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.

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

    Directory of Open Access Journals (Sweden)

    Stephen D Bentley


    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.

  15. Invasive Meningococcal Disease on the Workplaces: a systematic review. (United States)

    Riccò, Matteo; Vezzosi, Luigi; Odone, Anna; Signorelli, Carlo


    Background and aims of the work: Invasive Meningococcal Disease (IMD) represents a global health threat, and occupational settings have the potential to contribute to its spreading. Therefore, here we present the available evidences on the epidemiology of IMD on the workplaces. The following key words were used to explore PubMed: Neisseria meningitidis, meningococcus, meningococcal, invasive meningococcal disease, epidemiology, outbreaks, profession(al), occupation(al). We identified a total of 12 IMD cases among healthcare workers (HCW), 44 involving biological laboratory workers (BLW), 8 among school personnel, and eventually 27 from other settings, including 3 large industrial working populations. Eventual prognosis of BLW, particularly the case/fatality ratio, was dismal. As clustered in time and space, data about school cases as well as industrial cases seem to reflect community rather than occupational outbreaks. In general, we identified a common pattern for HCW and BLW, i.e. the exposure to droplets or aerosol containing N meningitidis in absence of appropriate personal protective equipment (PPE) and/or microbiological safety devices (MSD) (e.g. cabinets). Post-exposure chemoprophylaxis (PEC) was rarely reported by HCW (16.7%) workers, and never by BLW. Data regarding vaccination status were available only for a case, who had failed requested boosters. The risk for occupational transmission of IMD appears relatively low, possibly as a consequence of significant reporting bias, with the exception of HCW and BLW. Improved preventive measures should be implemented in these occupational groups, in order to improve the strict use of PPE and MSD, and the appropriate implementation of PEC.

  16. 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 (United States)

    Giuntini, Serena; Reason, Donald C.


    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. PMID:22064712

  17. Should corticosteroids be used in bacterial meningitis in children? (United States)

    Esposito, Susanna; Semino, Margherita; Picciolli, Irene; Principi, Nicola


    Bacterial meningitis is one of the most serious infections in infants and children, with considerable morbidity and mortality. Despite the spreading of conjugated vaccines against Haemophilus influenzae type b (Hib), the most important pneumococcal serotypes and serogroup C meningococcus has reduced the incidence of this infection in developed countries, it still remains a global public health problem and an important cause of mortality and disability. Whether corticosteroids should be used as a complementary therapy to antibacterials is still not clear because of the disparate findings from clinical trials and clinical evidence. The aim of this review is to analyze the available evidence on the impact of corticosteroid therapy in infants and children with bacterial meningitis in developed countries in order to define whether they should be added routinely in the empiric therapy of such disease. Our analysis concluded that in high-income countries dexamethasone has shown good results to prevent hearing loss in Hib meningitis if administered before or at the same time as the first dose of antibiotics. Dexamethasone should be evaluated in pneumococcal meningitis: it may be less beneficial in children with delayed presentation to medical attention and may be unfavourable in case of cephalosporin-resistant pneumococci. On the contrary, there is no evidence to recommend the use of corticosteroids in meningococcal meningitis. Further studies that take into account the epidemiologic changes of recent years, consider enrolment based on the onset of symptoms and evaluate outcomes such as hearing loss and neurologic sequelae with advanced techniques are urgently needed. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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

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    Kyriaki Tryfinopoulou

    Full Text Available 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.

  19. Hyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells. (United States)

    Brynjolfsson, Siggeir F; Henneken, Maren; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif


    Repeated immunizations with polysaccharide (PS) vaccines cause hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS booster on immune responses, frequency, and survival of PS-specific B-cell subpopulations in spleen and bone marrow. Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was injected daily intraperitoneally. MenC-PS-specific cells were labeled with fluorescent MenC-PS and phenotyped by flow cytometry. After MenC-PS booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(-)/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve hours after the MenC-PS booster, an increased frequency of apoptotic (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC-CRM(197) (P = .0286) or saline (P = .001) boosters. We demonstrated that the MenC-PS booster significantly reduced the frequency of newly activated MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into apoptosis. It shows directly that apoptosis of PS-specific memory cells is the cause of PS-induced hyporesponsiveness. These results should be taken into account prior to consideration of the use of PS vaccines.

  20. 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


    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.

  1. Epitope Mapping of a Monoclonal Antibody Directed against Neisserial Heparin Binding Antigen Using Next Generation Sequencing of Antigen-Specific Libraries.

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    Maria Domina

    Full Text Available We explore here the potential of a newly described technology, which is named PROFILER and is based on next generation sequencing of gene-specific lambda phage-displayed libraries, to rapidly and accurately map monoclonal antibody (mAb epitopes. For this purpose, we used a novel mAb (designated 31E10/E7 directed against Neisserial Heparin-Binding Antigen (NHBA, a component of the anti-group B meningococcus Bexsero® vaccine. An NHBA phage-displayed library was affinity-selected with mAb 31E10/E7, followed by massive sequencing of the inserts present in antibody-selected phage pools. Insert analysis identified an amino acid stretch (D91-A128 in the N-terminal domain, which was shared by all of the mAb-enriched fragments. Moreover, a recombinant fragment encompassing this sequence could recapitulate the immunoreactivity of the entire NHBA molecule against mAb 31E10/E7. These results were confirmed using a panel of overlapping recombinant fragments derived from the NHBA vaccine variant and a set of chemically synthetized peptides covering the 10 most frequent antigenic variants. Furthermore, hydrogen-deuterium exchange mass-spectrometry analysis of the NHBA-mAb 31E10/E7 complex was also compatible with mapping of the epitope to the D91-A128 region. Collectively, these results indicate that the PROFILER technology can reliably identify epitope-containing antigenic fragments and requires considerably less work, time and reagents than other epitope mapping methods.

  2. Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013 (United States)

    Bröker, Michael; Emonet, Stéphane; Fazio, Cecilia; Jacobsson, Susanne; Koliou, Maria; Kuusi, Markku; Pace, David; Paragi, Metka; Pysik, Alexander; Simões, Maria João; Skoczynska, Anna; Stefanelli, Paola; Toropainen, Maija; Taha, Muhamed-Kheir; Tzanakaki, Georgina


    Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogoup A has been prevalent in the African “meningitis belt” whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journal1, an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions. PMID:26036710

  3. Getting it right from birth to kindergarten: what's new in the Rourke Baby Record? (United States)

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


    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.

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

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    David J. Dowling


    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.

  5. 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. (United States)

    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


    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.

  6. Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake. (United States)

    Malhi, Gurtej; Rumman, Amir; Thanabalan, Reka; Croitoru, Kenneth; Silverberg, Mark S; Hillary Steinhart, A; Nguyen, Geoffrey C


    Immunomodulators and biological agents, used to treat inflammatory bowel disease [IBD], are associated with an increased risk of infection, including vaccine-preventable infections. We assessed patient attitudes towards vaccination, knowledge of vaccine recommendations, and uptake of recommended vaccines. Patients attending IBD clinics completed a self-administered, structured, paper-based questionnaire. We collected demographic data, medical and immunisation history, self-reported patient uptake, knowledge, and perceptions of childhood and adult vaccinations. The prevalence of treatment with biologicals, steroids, thiopurines, and methotrexate among the 300 respondents were 37.3%, 16.0%, 16.0%, and 5.7%, respectively. Self-reported vaccine completion was reported by 45.3% of patients. Vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for herpes zoster, and 11.0% for herpes papilloma virus [females only]. Significant predictors of vaccine completion were annual vaccination review by family physician (odds ratio [OR] = 1.82) or gastroenterologist [OR = 1.72], current steroid use [OR = 1.28], and current or prior treatment with biologicals [OR = 1.42]. The majority of patients reported that the primary responsibility to ensure vaccine completion lies with the patient [41.7%] and the family physician [32.3%]. Uncertainty about indications, fears of side effects, and concerns regarding vaccine safety were the most commonly reported reasons for non-uptake [22.0%, 20.7%, and 5.3%, respectively]. Uptake of recommended vaccines among IBD patients is suboptimal. Annual vaccination reviews by both family physician and gastroenterologist may improve vaccine uptake. Interventions targeted at improving vaccination uptake in IBD patients are needed. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All

  7. 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


    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.

  8. 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


    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.

  9. The role of apolipoprotein N-acyl transferase, Lnt, in the lipidation of factor H binding protein of Neisseria meningitidis strain MC58 and its potential as a drug target. (United States)

    da Silva, R A G; Churchward, C P; Karlyshev, A V; Eleftheriadou, O; Snabaitis, A K; Longman, M R; Ryan, A; Griffin, R


    The level of cell surface expression of the meningococcal vaccine antigen, Factor H binding protein (FHbp) varies between and within strains and this limits the breadth of strains that can be targeted by FHbp-based vaccines. The molecular pathway controlling expression of FHbp at the cell surface, including its lipidation, sorting to the outer membrane and export, and the potential regulation of this pathway have not been investigated until now. This knowledge will aid our evaluation of FHbp vaccines. A meningococcal transposon library was screened by whole cell immuno-dot blotting using an anti-FHbp antibody to identify a mutant with reduced binding and the disrupted gene was determined. In a mutant with markedly reduced binding, the transposon was located in the lnt gene which encodes apolipoprotein N-acyl transferase, Lnt, responsible for the addition of the third fatty acid to apolipoproteins prior to their sorting to the outer membrane. We provide data indicating that in the Lnt mutant, FHbp is diacylated and its expression within the cell is reduced 10 fold, partly due to inhibition of transcription. Furthermore the Lnt mutant showed 64 fold and 16 fold increase in susceptibility to rifampicin and ciprofloxacin respectively. We speculate that the inefficient sorting of diacylated FHbp in the meningococcus results in its accumulation in the periplasm inducing an envelope stress response to down-regulate its expression. We propose Lnt as a potential novel drug target for combination therapy with antibiotics. This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit © 2016 The British Pharmacological Society.

  10. Adapting immunisation schedules for children undergoing chemotherapy. (United States)

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


    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.

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

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    Beth Holder


    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.

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

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


    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.


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    Muljati Prijanto


    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

  14. 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. (United States)

    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


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

  15. Vaccination coverage among social and healthcare workers in ten countries of Samu-social international sites. (United States)

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


    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

  16. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. (United States)

    Karussis, Dimitrios; Petrou, Panayiota


    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  17. Design and evaluation of meningococcal vaccines through structure-based modification of host and pathogen molecules.

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    Steven Johnson

    Full Text Available Neisseria meningitis remains a leading cause of sepsis and meningitis, and vaccines are required to prevent infections by this important human pathogen. Factor H binding protein (fHbp is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator, fH. As the high affinity interaction between fHbp and fH could impair immune responses, we sought to identify non-functional fHbps that could act as effective immunogens. This was achieved by alanine substitution of fHbps from all three variant groups (V1, V2 and V3 fHbp of the protein; while some residues affected fH binding in each variant group, the distribution of key amino underlying the interaction with fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations to the differences in the precise nature of their interactions with fH, and the instability of the V2 protein. To develop transgenic models to assess the efficacy of non-functional fHbps, we determined the structural basis of the low level of interaction between fHbp and murine fH; in addition to changes in amino acids in the fHbp binding site, murine fH has a distinct conformation compared with the human protein that would sterically inhibit binding to fHbp. Non-functional V1 fHbps were further characterised by binding and structural studies, and shown in non-transgenic and transgenic mice (expressing chimeric fH that binds fHbp and precisely regulates complement system to retain their immunogenicity. Our findings provide a catalogue of non-functional fHbps from all variant groups that can be included in new generation meningococcal vaccines, and establish proof-in-principle for clinical studies to compare their efficacy with wild-type fHbps.

  18. Design and evaluation of meningococcal vaccines through structure-based modification of host and pathogen molecules. (United States)

    Johnson, Steven; Tan, Lionel; van der Veen, Stijn; Caesar, Joseph; Goicoechea De Jorge, Elena; Harding, Rachel J; Bai, Xilian; Exley, Rachel M; Ward, Philip N; Ruivo, Nicola; Trivedi, Kaushali; Cumber, Elspeth; Jones, Rhian; Newham, Luke; Staunton, David; Ufret-Vincenty, Rafael; Borrow, Ray; Pickering, Matthew C; Lea, Susan M; Tang, Christoph M


    Neisseria meningitis remains a leading cause of sepsis and meningitis, and vaccines are required to prevent infections by this important human pathogen. Factor H binding protein (fHbp) is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator, fH. As the high affinity interaction between fHbp and fH could impair immune responses, we sought to identify non-functional fHbps that could act as effective immunogens. This was achieved by alanine substitution of fHbps from all three variant groups (V1, V2 and V3 fHbp) of the protein; while some residues affected fH binding in each variant group, the distribution of key amino underlying the interaction with fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations to the differences in the precise nature of their interactions with fH, and the instability of the V2 protein. To develop transgenic models to assess the efficacy of non-functional fHbps, we determined the structural basis of the low level of interaction between fHbp and murine fH; in addition to changes in amino acids in the fHbp binding site, murine fH has a distinct conformation compared with the human protein that would sterically inhibit binding to fHbp. Non-functional V1 fHbps were further characterised by binding and structural studies, and shown in non-transgenic and transgenic mice (expressing chimeric fH that binds fHbp and precisely regulates complement system) to retain their immunogenicity. Our findings provide a catalogue of non-functional fHbps from all variant groups that can be included in new generation meningococcal vaccines, and establish proof-in-principle for clinical studies to compare their efficacy with wild-type fHbps.

  19. Echocardiography and ultrasound dopplerography assessment of central and peripheral hemodynamics in children with septic shock

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    V.V. Yevtushenko


    Full Text Available Background. The severe course of sepsis is usually associated with the development of septic shock and multiple organ failure. For effective treatment, it is recommended to perform instrumental monitoring of preload, contractile capacity of the heart and tissue perfusion. We aimed to evaluate changes in central and peripheral hemodynamics by echocardiography and Doppler ultrasound in children with septic shock. Materials and methods. A retrospective study of cases of septic shock in children aged 0 to 18 years who underwent treatment in the intensive care unit was conducted. Patients were monitored for central and peripheral hemodynamics by echocardiography and Doppler ultrasound. The initial study of hemodynamic parameters was carried out over the first 3 hours after hospitalization. The second study was carried out in 24–36 hours after the hospitalization. The third study was conducted in the period of convalescence within 24–48 hours after the withdrawal of sympathomimetic drugs. Results. Thirty-four cases of sepsis associated with septic shock were investigated. In 24 (70.6 % patients, the etiological factor was meningococcus, in 1 (2.9 % staphylococcus, and in 9 (26.5 % no aetiology was established. In 6 children from the study group fatal outcome occurred. Values of mean blood pressure, ejection fraction, peripheral resistance were relatively lower in the acute shock period, and increased after stabilization of hemodynamics. Evaluation of peripheral blood circulation at admission showed decreased diastolic velocity in abdominal aorta and upper mesenteric artery and systolic velocity in posterior tibial artery. The results of initial investigation demonstrated that 44.1 % patients had increased cardiac output along with decreased systemic vascular resistance (‘warm shock’, and just 8.8 % had features of ‘cold shock’ (decreased cardiac output and increased vascular resistance. The fatal course of the disease was associated with

  20. Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2006-2010. (United States)

    Naidu, Latika; Chiu, Clayton; Habig, Andrew; Lowbridge, Christopher; Jayasinghe, Sanjay; Wang, Han; McIntyre, Peter; Menzies, Robert


    This report outlines the major positive impacts of vaccines on the health of Aboriginal and Torres Strait Islander people from 2007 to 2010, as well as highlighting areas that require further attention. Hepatitis A disease is now less common in Aboriginal and Torres Strait Islander children than in their non-Indigenous counterparts. Hepatitis A vaccination for Aboriginal and Torres Strait Islander children was introduced in 2005 in the high incidence jurisdictions of the Northern Territory, Queensland, South Australia and Western Australia. In 2002–2005, there were 20 hospitalisations for hepatitis A in Aboriginal and Torres Strait Islander children agedtypes prior to vaccine introduction, the decline in total IPD notifications has been less marked in Aboriginal and Torres Strait Islander children than in other children. Higher valency vaccines (10vPCV and 13vPCV) which replaced 7vPCV from 2011 are likely to result in a greater impact on IPD and potentially also non-invasive disease, although disease caused by non-vaccine serotypes appears likely to be an ongoing problem. Among Aboriginal and Torres Strait Islander people aged ≥50 years, there have been recent increases in IPD, which appear related to low vaccination coverage and highlight the need for improved coverage in this high-risk target group. Since routine meningococcal C vaccination for infants and the high-school catch-up program were implemented in 2003, there has been a significant decrease in cases caused by serogroup C. However, the predominant serogroup responsible for disease remains serogroup B, and Aboriginal and Torres Strait Islander children have significantly higher incidence of serogroup B disease than other children. A vaccine against meningococcus type B has now been licensed in Australia. The decline in severe rotavirus disease after vaccine introduction in 2007 was less marked in Aboriginal and Torres Strait Islander children than in other children. By far the highest hospitalisation

  1. A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults. (United States)

    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


    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

  2. 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


    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.

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

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    Ricardo Becker Feijó


    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.

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

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    Chang Hsiu-Li


    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

  5. 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


    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


    Zinsser, Hans; Parker, Julia T.


    When filtered alkaline extracts of pulverized bacteria of several varieties are precipitated with acid in the cold, boiled with acid, and all materials thrown down by these procedures removed, there remains a small amount of an alcohol-precipitable material which no longer gives any of the ordinary chemical reactions for proteins, such as the biuret, Hopkins-Cole, Millon, and sulfosalicylic acid reactions. The only protein reaction usually given by this material is a very weak xanthoproteic reaction. Nevertheless, the material, which is, as far as we can determine at present, free from coagulable protein, is specifically precipitable by homologous antiserum and gives specific complement fixation reactions. Such material can also be obtained from organisms like the influenza bacillus, pneumococcus, and meningococcus by extraction without preliminary grinding of the bacteria, and is present in filtrates of young and old broth cultures of the organisms. We believe that these acid- and heat-resistant antigenic materials are analogous to tuberculin and to the pneumococcus substances with which Dochez and Avery (6) made their observations some years ago. The stability of these substances is considerable and was investigated particularly because we thought this represented an indirect method of eliminating the possibility of their protein nature. In all cases boiling in a reflux condenser at an acid reaction ranging from pH 5 to 6 for 1 hour failed to destroy the antigenic specificity of the residue antigens. After such treatment satisfactory and specific precipitation reactions could be obtained. Similar boiling in alkaline reactions, however, destroyed the precipitability of staphylococcus and influenza residues. Subjected to autoclave digestion at an acid reaction of pH 5.4 for 1 hour at from three to four atmospheres, none of the antigenic residues investigated, except that obtained from the influenza bacillus, were destroyed. The pneumococcus and tubercle bacillus

  7. 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


    (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