Clinical characteristics and public health management of invasive meningococcal group W disease in the East Midlands region of England, United Kingdom, 2011 to 2013.

PubMed

Bethea, Jane; Makki, Sophia; Gray, Steve; MacGregor, Vanessa; Ladhani, Shamez

2016-06-16

In England and Wales, meningococcal disease caused by group W has historically been associated with outbreaks of disease among travellers to high-risk countries. Following a large outbreak associated with travel to the Hajj in 2000, the number of cases declined and, in 2008, only 19 laboratory-confirmed cases were identified nationally. In 2013, in the East Midlands region of England, eight cases of meningococcal disease caused by this serogroup were recorded, compared with six from 2011 to 2012. To explore this further, data for all cases with a date of onset between 1 January 2011 and 31 December 2013 were collected. Data collected included geographical location, clinical presentation and outcome. Fourteen cases were identified; two died as a result of their illness and two developed long-term health problems. No commonality in terms of geographical location, shared space or activities was identified, suggesting that group W is circulating endemically with local transmission. Clinical presentation was variable. Half presented with symptoms not typical of a classical meningococcal disease, including two cases of cellulitis, which may have implications for clinicians, in terms of timely identification and treatment, and public health specialists, for offering timely antibiotic chemoprophylaxis to close contacts. This article is copyright of The Authors, 2016.

Immunogenicity and safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) administered to adults aged 56 Years and older: results of an open-label, randomized, controlled trial.

PubMed

Dbaibo, Ghassan; El-Ayoubi, Nabil; Ghanem, Soha; Hajar, Farah; Bianco, Veronique; Miller, Jacqueline M; Mesaros, Narcisa

2013-05-01

The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults >55 years of age. To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix™, GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax™ GlaxoSmithKline, Belgium) in adults >55 years of age. This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with MenACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of ≥1:32 in initially seronegative subjects (rSBA titer <1:8); ≥4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and ≥2-fold increase in subjects with pre-vaccination rSBA titers ≥1:128]. The percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events

Consensus building and recommendations based on the available epidemiology of meningococcal disease in Gulf Cooperation Council States.

PubMed

Memish, Ziad A; Shibl, Atef M

2011-03-01

The Gulf Cooperation Council (GCC) States share concerns about meningococcal disease, particularly in association with the Hajj and Umrah pilgrimages, which have been connected with outbreaks within the Kingdom of Saudi Arabia and among contacts of the pilgrims in their countries of origin. Currently, the most prevalent meningococcal serogroup in the GCC States is W-135. Although vaccination with polysaccharide vaccines has protected pilgrims and their close contacts from invasive disease, the potential availability of novel conjugate vaccines, such as the one currently used for vaccination of military personnel in the Kingdom of Saudi Arabia, prompted an evaluation of disease epidemiology in the region. For several countries, published data on recent epidemiology are not available. We report findings from a meeting of the GCC States Meningitis Study Group, which comprised experts from the Kingdom of Saudi Arabia, the Kingdom of Bahrain, Kuwait, Qatar, the Sultanate of Oman, and the United Arab Emirates. These experts provided an update on epidemiology and current vaccination practices in the GCC States, and discussed new approaches to more effective disease prevention. Copyright © 2011 Elsevier Ltd. All rights reserved.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study.

PubMed

Tully, Joanna; Viner, Russell M; Coen, Pietro G; Stuart, James M; Zambon, Maria; Peckham, Catherine; Booth, Clare; Klein, Nigel; Kaczmarski, Ed; Booy, Robert

2006-02-25

To examine biological and social risk factors for meningococcal disease in adolescents. Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. Six contiguous regions of England, which represent some 65% of the country's population. 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

PubMed Central

Tully, Joanna; Viner, Russell M; Coen, Pietro G; Stuart, James M; Zambon, Maria; Peckham, Catherine; Booth, Clare; Klein, Nigel; Kaczmarski, Ed; Booy, Robert

2006-01-01

Objective To examine biological and social risk factors for meningococcal disease in adolescents. Design Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. Setting Six contiguous regions of England, which represent some 65% of the country's population. Participants 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. Methods Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. Results 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. Conclusions Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority. PMID:16473859

Meningococcal Disease

MedlinePlus

... from UMass Amherst . Oregon State University Oregon State University (OSU) has an ongoing outbreak of serogroup B meningococcal disease. Students should check with OSU about requirements to get ...

Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease.

PubMed

Tsang, Raymond S W; Ahmad, Tauqeer; Tyler, Shaun; Lefebvre, Brigitte; Deeks, Shelley L; Gilca, Rodica; Hoang, Linda; Tyrrell, Gregory; Van Caeseele, Paul; Van Domselaar, Gary; Jamieson, Frances B

2018-04-01

This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

How complete and accurate is meningococcal disease notification?

PubMed

Breen, E; Ghebrehewet, S; Regan, M; Thomson, A P J

2004-12-01

Effective public health control of meningococcal disease (meningococcal meningitis and septicaemia) is dependent on complete, accurate and speedy notification. Using capture-recapture techniques this study assesses the completeness, accuracy and timeliness of meningococcal notification in a health authority. The completeness of meningococcal disease notification was 94.8% (95% confidence interval 93.2% to 96.2%); 91.2% of cases in 2001 were notified within 24 hours of diagnosis, but 28.0% of notifications in 2001 were false positives. Clinical staff need to be aware of the public health implications of a notification of meningococcal disease, and of failure of, or delay in notification. Incomplete or delayed notification not only leads to inaccurate data collection but also means that important public health measures may not be taken. A clinical diagnosis of meningococcal disease should be carefully considered between the clinician and the consultant in communicable disease control (CCDC). Otherwise, prophylaxis may be given unnecessarily, disease incidence inflated, and the benefits of control measures underestimated. Consultants in communicable disease control (CCDCs), in conjunction with clinical staff, should de-notify meningococcal disease if the diagnosis changes.

Determinants of case fatality rates of meningococcal disease during outbreaks in Makkah, Saudi Arabia, 1987-97.

PubMed Central

El Bushra, H. E.; Hassan, N. M.; Al-Hamdan, N. A.; Al-Jeffri, M. H.; Turkistani, A. M.; Al-Jumaily, A.; Ali, M. A.; Rahama, A. M.

2000-01-01

We studied case-fatality rates (CFRs) among cases of meningococcal disease (MCD) admitted to Makkah (Saudi Arabia) hospitals during the period 1988-97. Of 483 cases, 431 (89.2%) were due to strains of serogroup A, 31 (6.4%) to serogroup W135, 16 (3.3%) to serogroup C, and 5 (10%) to serogroup B. Eighty-one patients died (case fatality rate (CFR)) 16.8%, 95% CI 13.5%, 20.4%). The CFR in infections due to serogroup A strains was 14.8%, and for other serogroups it was 32.7% (95% CI 20.3%, 47.1%). The CFR of MCD due to N. meningitidis serogroup A increased steadily with age (P<0.05). Seeking first medical help at a foreign Hajj medical mission and being treated in a non-specialized hospital were associated with a higher case fatality rate. PMID:11218206

Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

PubMed

Borrow, Ray; Lee, Jin-Soo; Vázquez, Julio A; Enwere, Godwin; Taha, Muhamed-Kheir; Kamiya, Hajime; Kim, Hwang Min; Jo, Dae Sun

2016-11-21

The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region.Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W. Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public. Copyright © 2016. Published by Elsevier Ltd.

Invasive meningococcal disease epidemiology and control measures: a framework for evaluation.

PubMed

Caro, J Jaime; Möller, Jörgen; Getsios, Denis; Coudeville, L; El-Hadi, Wissam; Chevat, Catherine; Nguyen, Van Hung; Caro, Ingrid

2007-06-29

Meningococcal disease can have devastating consequences. As new vaccines emerge, it is necessary to assess their impact on public health. In the absence of long-term real world data, modeling the effects of different vaccination strategies is required. Discrete event simulation provides a flexible platform with which to conduct such evaluations. A discrete event simulation of the epidemiology of invasive meningococcal disease was developed to quantify the potential impact of implementing routine vaccination of adolescents in the United States with a quadrivalent conjugate vaccine protecting against serogroups A, C, Y, and W-135. The impact of vaccination is assessed including both the direct effects on individuals vaccinated and the indirect effects resulting from herd immunity. The simulation integrates a variety of epidemiologic and demographic data, with core information on the incidence of invasive meningococcal disease and outbreak frequency derived from data available through the Centers for Disease Control and Prevention. Simulation of the potential indirect benefits of vaccination resulting from herd immunity draw on data from the United Kingdom, where routine vaccination with a conjugate vaccine has been in place for a number of years. Cases of disease are modeled along with their health consequences, as are the occurrence of disease outbreaks. When run without a strategy of routine immunization, the simulation accurately predicts the age-specific incidence of invasive meningococcal disease and the site-specific frequency of outbreaks in the Unite States. 2,807 cases are predicted annually, resulting in over 14,000 potential life years lost due to invasive disease. In base case analyses of routine vaccination, life years lost due to infection are reduced by over 45% (to 7,600) when routinely vaccinating adolescents 12 years of age at 70% coverage. Sensitivity analyses indicate that herd immunity plays an important role when this population is targeted for

A cluster of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W among university students, France, February to May 2017

PubMed Central

Bassi, Clément; Taha, Muhamed-Kheir; Merle, Christian; Hong, Eva; Lévy-Bruhl, Daniel; Barret, Anne-Sophie; Mounchetrou Njoya, Ibrahim

2017-01-01

Between February and May 2017, two cases of invasive meningococcal disease caused by a new, rapidly expanding serogroup W meningococci variant were reported among students of an international university in Paris. Bacteriological investigations showed that isolates shared identical genotypic formula (W:P1.5,2:F1–1:cc11) and belonged to the South American/UK lineage. A vaccination campaign was organised that aimed at preventing new cases linked to potential persistence of the circulation of the bacteria in the students. PMID:28749333

A Decade of Invasive Meningococcal Disease Surveillance in Poland

PubMed Central

Skoczyńska, Anna; Waśko, Izabela; Kuch, Alicja; Kadłubowski, Marcin; Gołębiewska, Agnieszka; Foryś, Małgorzata; Markowska, Marlena; Ronkiewicz, Patrycja; Wasiak, Katarzyna; Kozińska, Aleksandra; Matynia, Bożena; Hryniewicz, Waleria

2013-01-01

Background Neisseria meningitidis is a leading etiologic agent of severe invasive disease. The objective of the study was to characterise invasive meningococcal disease (IMD) epidemiology in Poland during the last decade, based on laboratory confirmed cases. Methods The study encompassed all invasive meningococci collected between 2002 and 2011 in the National Reference Centre for Bacterial Meningitis. The isolates were re-identified and characterised by susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique was used for meningococcal identification directly from clinical materials. Results In the period studied, 1936 cases of IMD were confirmed, including 75.6% identified by culture. Seven IMD outbreaks, affecting mostly adolescents, were reported; all were caused by serogroup C meningococci of ST-11. The highest incidence was observed among children under one year of age (15.71/100,000 in 2011). The general case fatality rate in the years 2010–2011 was 10.0%. Meningococci of serogroup B, C, Y and W-135 were responsible for 48.8%, 36.6%, 1.2% and 1.2% of cases, respectively. All isolates were susceptible to third generation cephalosporins, chloramphenicol, ciprofloxacin, and 84.2% were susceptible to penicillin. MLST analysis (2009–2011) revealed that among serogroup B isolates the most represented were clonal complexes (CC) ST-32CC, ST-18CC, ST-41/44CC, ST-213CC and ST-269CC, and among serogroup C: ST-103CC, ST-41/44CC and ST-11CC. Conclusions The detection of IMD in Poland has changed over time, but observed increase in the incidence of the disease was mostly attributed to changes in the surveillance system including an expanded case definition and inclusion of data from non-culture diagnostics. PMID:23977184

The Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection.

PubMed

Borrow, Ray; Alarcón, Pedro; Carlos, Josefina; Caugant, Dominique A; Christensen, Hannah; Debbag, Roberto; De Wals, Philippe; Echániz-Aviles, Gabriela; Findlow, Jamie; Head, Chris; Holt, Daphne; Kamiya, Hajime; Saha, Samir K; Sidorenko, Sergey; Taha, Muhamed-Kheir; Trotter, Caroline; Vázquez Moreno, Julio A; von Gottberg, Anne; Sáfadi, Marco A P

2017-04-01

The 2015 Global Meningococcal Initiative (GMI) meeting discussed the global importance of meningococcal disease (MD) and its continually changing epidemiology. Areas covered: Although recent vaccination programs have been successful in reducing incidence in many countries (e.g. Neisseria meningitidis serogroup [Men]C in Brazil, MenA in the African meningitis belt), new clones have emerged, causing outbreaks (e.g. MenW in South America, MenC in Nigeria and Niger). The importance of herd protection was highlighted, emphasizing the need for high vaccination uptake among those with the highest carriage rates, as was the need for boosters to maintain individual and herd protection following decline of immune response after primary immunization. Expert commentary: The GMI Global Recommendations for Meningococcal Disease were updated to include a recommendation to enable access to whole-genome sequencing as for surveillance, guidance on strain typing to guide use of subcapsular vaccines, and recognition of the importance of advocacy and awareness campaigns.

Meningococcal B vaccination: real-world experience and future perspectives

PubMed Central

Kuhdari, Parvanè; Valente, Nicoletta; Gabutti, Giovanni

2016-01-01

Invasive meningococcal disease (IMD) represents a severe risk for health. It can be considered the most dangerous vaccine-preventable disease due to the high probability of related permanent sequelae and death. The introduction in many countries of the conjugate vaccines against A, C, W135, and Y meningococcal serogroups influenced significantly the impact of the disease. Recently, the difficulties in obtaining an effective vaccine against meningococcal serogroup B (MenB) have been get over through the reverse vaccinology, enabling the recognition of some antigens providing a response against most of circulating MenB strains worldwide. The new 4cMenB vaccine is recommended in Europe, Canada, Australia, the USA, and some Latin American countries. Even if sound data on efficacy and safety profile are available, the results in terms of effectiveness are still limited. The management of the MenB outbreaks in two US universities demonstrated the ability to quickly achieve high vaccination coverage rates and no new cases among immunized subjects were assessed. It is desirable that the opportunity to complete preventive intervention against IMD offered by the new 4cMenB vaccine should be recognized and that this vaccine is included in the vaccination schedule to complete the panel of immunization against Neisseria meningitidis. PMID:27309042

Correlation between serum bactericidal activity against Neisseria meningitidis serogroups A, C, W-135 and Y measured using human versus rabbit serum as the complement source.

PubMed Central

CJ, Gill; S, Ram; JA, Welsch; L, DeTora; A, Anemona

2014-01-01

The surrogate of protection against invasive meningococcal disease is the presence of serum bactericidal activity (SBA) at a titer ≥4 in an assay using human serum as the complement source (hSBA). However, for various practical and logistical reasons, many meningococcal vaccines in use today were licensed based on a modified SBA assay that used baby rabbit serum as the complement source (rSBA). To assess the strength of correlation between the two assay systems for serogroups A, C, W-135 and Y, we analyzed a subset of samples from adolescent subjects enrolled in a Phase II study of Novartis’ MenACWY-CRM conjugate vaccine vs. an ACWY polysaccharide vaccine; samples were analyzed in parallel using hSBA and rSBA. We compared geometric mean titers (GMTs), calculated Pearson correlation coefficients between paired hSBA and rSBA results, and calculated sensitivity/specificity and likelihood ratios for an rSBA ≥8 or ≥128 for classifying hSBA ≥4, taking hSBA as the ‘gold standard’. Correlations between hSBA and rSBA ranged from 0.46 to 0.78 for serogroup C, but were weaker for serogroups A, W-135 and Y (range -0.15 to 0.57). In post vaccination samples, nearly all subjects had rSBA titers ≥8, though up to 15% remained seronegative by hSBA. In post vaccination settings, rSBA titers at ≥8 or ≥128 was highly sensitive for an hSBA titer ≥4, but non-specific. In conclusion, results generated by rSBA did not accurately classify serostatus according to hSBA for serogroups A, W-135 and Y. PMID:22075087

[Invasive meningococcal disease in the Czech Republic - analysis of the epidemiological situation and vaccination strategy recommendations].

PubMed

Křížová, Pavla; Vacková, Zuzana; Musílek, Martin; Kozáková, Jana

2013-12-01

Analysis of invasive meningococcal disease (IMD) surveillance data including molecular epidemio-logy data. Vaccination strategy recommendations based on the current epidemiological situation of IMD in the Czech Republic and availability of meningococcal vaccines. IMD surveillance data are compiled by the National Reference Laboratory for Meningococcal Disease (NRL) from routinely reported data and NRL data after clearing out duplicate data. Neisseria meningitidis (N.m.) isolates referred to the NRL are confirmed and characterized in detail according to internationally validated methods. The current epidemiological situation of IMD is relatively favourable - the incidence rates have been below 1/100,000 population for several years, but show a slightly upward trend over more than 40-year period (1970-2012). A return to the typical prevalence of serogroup B accounting for up to 75% of cases has recently been shown. In this context, the upward trend in IMD caused by serogroup Y associated with a high case fatality rate in the Czech Republic cannot be overseen or even underestimated. The hypervirulent clonal complex cc11 characteristic of N.m.C:2a:P1.2,5 prevailed in this country between 1993 and 2004, but decreased in the following years and currently, hypervirulent clonal complexes characteristic of N.m.B (cc18, cc32, cc41/44, and cc269) are the most common in the Czech Republic. The average overall case fatality rate in the Czech Republic is 10%, but varies between causative serogroups: the highest case fatality rate has been caused by serogroup Y (16.7% ), followed by serogroup C (12.3%), and serogroup W135 (11.7%), while serogroup B only accounts for a case fatality rate of 7.8%. In the age group under one year, the incidence of IMD caused by serogroup B remains three to five times as high as in the age groups 1-4 years and 15-19 years throughout the surveillance period. The highest numbers of IMD cases caused by serogroup B have been reported in 3-7-month

Meningococcal disease in the Middle East and Africa: Findings and updates from the Global Meningococcal Initiative.

PubMed

Borrow, Ray; Caugant, Dominique A; Ceyhan, Mehmet; Christensen, Hannah; Dinleyici, Ener Cagri; Findlow, Jamie; Glennie, Linda; Von Gottberg, Anne; Kechrid, Amel; Vázquez Moreno, Julio; Razki, Aziza; Smith, Vincent; Taha, Muhamed-Kheir; Tali-Maamar, Hassiba; Zerouali, Khalid

2017-07-01

The Global Meningococcal Initiative (GMI) has recently considered current issues in Middle Eastern and African countries, and produced two recommendations: (i) that vaccination of attendees should be considered for some types of mass-gathering events, as some countries mandate for the Hajj, and (ii) vaccination of people with human immunodeficiency virus should be used routinely, because of increased meningococcal disease (MD) risk. Differences exist between Middle Eastern and African countries regarding case and syndrome definitions, surveillance, and epidemiologic data gaps. Sentinel surveillance provides an overview of trends and prevalence of different capsular groups supporting vaccine selection and planning, whereas cost-effectiveness decisions require comprehensive disease burden data, ideally counting every case. Surveillance data showed importance of serogroup B MD in North Africa and serogroup W expansion in Turkey and South Africa. Success of MenAfriVac ® in the African "meningitis belt" was reviewed; the GMI believes similar benefits may follow development of a low-cost meningococcal pentavalent vaccine, currently in phase 1 clinical trial, by 2022. The importance of carriage and herd protection for controlling invasive MD and the importance of advocacy and awareness campaigns were also highlighted. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Implementation of MenACWY vaccination because of ongoing increase in serogroup W invasive meningococcal disease, the Netherlands, 2018.

PubMed

Knol, Mirjam J; Ruijs, Wilhelmina Lm; Antonise-Kamp, Laura; de Melker, Hester E; van der Ende, Arie

2018-04-01

The annual incidence rate of serogroup W invasive meningococcal disease in the Netherlands increased from < 0.05/100,000 (n < 10) before 2015 to 0.5/100,000 (n = 80) in 2017. Most isolates (94%) belong to clonal complex 11. The incidence rate is highest among  < 5 year-olds and 15-24 year-olds. The case fatality rate was 12% (17/138) in 2015-2017. From May 2018, MenACWY vaccination replaces MenC vaccination at age 14 months and from October 2018, 13-14 year-olds are offered MenACWY vaccination.

Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Cohn, Amanda C; MacNeil, Jessica R; Clark, Thomas A; Ortega-Sanchez, Ismael R; Briere, Elizabeth Z; Meissner, H Cody; Baker, Carol J; Messonnier, Nancy E

2013-03-22

Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for

Meningococcal Disease: Information for Teens and College Students

MedlinePlus

... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... limb amputation, or lifelong problems with the nervous system. How is meningococcal disease treated? Meningococcal disease is ...

Meningococcal vaccination for international travellers from Greece visiting developing countries.

PubMed

Pavli, Androula; Katerelos, Panagiotis; Smeti, Paraskevi; Maltezou, Helena C

2016-01-01

Meningococcal meningitis is a serious disease. Travel-associated infection for the general traveller is low; however regular epidemics in indigenous population, particularly in sub-Saharan Africa are responsible for significant morbidity and mortality. Our aim was to assess meningococcal vaccination for international travellers from Greece. A prospective questionnaire-based study was conducted during 2009-2013. A total of 5283 travellers were studied (median age: 39.2 years); Meningococcal tetravalent vaccine (A,C,W135,Y) was delivered to 1150 (21.8%) of them. Of those who travelled to the Middle East and sub-Saharan Africa, 73.1% and 21.2% received meningococcal vaccine, respectively. Of those travellers who travelled to sub-Saharan Africa from November to June and from July to October, 22.1% and 20.6% were vaccinated with meningococcal vaccine, respectively. Of all travellers who travelled for <1 month and ≥1 month, 23.3%, and 20.5%, were vaccinated, respectively. Meningococcal vaccine was administered to 95.3% of pilgrims, 17.4% of those visiting friends and relatives (VFRs), 16.7% of those who travelled for recreation, and 13.8% of those who travelled for work. Of travellers who stayed in urban, in rural, and in urban and rural areas, 32%, 11.6% and 12.7% were vaccinated, respectively. Meningococcal vaccine was delivered to 29.2%, 21.1%, 19.4% and 5.1% of those who stayed in hotels, at local people's home, in camps, and on ships, respectively. The association of meningococcal vaccine administration with the destination, duration and purpose of travel, area of stay and type of accommodation was statistically significant. There is a need to improve meningococcal vaccine recommendations for travellers from Greece, particularly for high risk populations, such as VFRs, business travellers and those visiting sub-Saharan Africa especially during the dry season. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parental smoking, socioeconomic factors, and risk of invasive meningococcal disease in children: a population based case-control study

PubMed Central

Kriz, P; Bobak, M; Kriz, B

2000-01-01

AIMS—To investigate the effects of parental smoking, socioeconomic characteristics, and indoor environment on the risk of invasive meningococcal disease in children.
METHODS—Population based case-control study. A total of 68 incident cases of invasive meningococcal disease in children less than 15 years old were compared with 135 controls selected from the same school and matched for year of birth, sex, and place of residence. Information on exposures was obtained in interviews with parents.
RESULTS—Invasive meningococcal disease was strongly associated with parental smoking; rate ratios adjusted for socioeconomic factors were 3.5 (95% confidence interval 1.4-8.7) for smoking of mother, 3.2 (1.5-6.9) for smoking of father, and 2.7 (1.3-5.4) for every 20 cigarettes smoked at home on an average day. The risk of the disease was strongly inversely related to maternal education and, less strongly, to ownership of a car and of a weekend house, father's education, crowding, and the number of siblings, but these associations were reduced or eliminated in multivariate models. The type of heating and cooking (used as proxies for indoor air pollution) were not associated with the disease.
CONCLUSION—The risk of invasive meningococcal disease in children is strongly influenced by parental smoking and unfavourable socioeconomic circumstances.

 PMID:10906015

Epidemiology of Meningococcal Disease in Northeastern Africa

DTIC Science & Technology

1987-01-01

etiology. The male/ female ratio of j the confimed meningococcal patients was 1:3; only IS% were less than 5 years of age while 50% were between 5 and 14...case isolates belong to serogroup A, and most of the meningococcal cases are in children above the age of 5 years. The male-to- female case ratio is...Walsdan, MW. H., Salim, S. A., Hissa, MW. N., Gawaod, A. A., Ralkha, A. S., Sippel, J. E., Hablas, R.9 Sanborn, W. R., Kassem , N. M., Riad, S. M., and

Meningococcal disease awareness and meningoccocal vaccination among Greek students planning to travel abroad.

PubMed

Pavli, Androula; Katerelos, Panagiotis; Maltezou, Helena C

2017-06-09

Objective Students living in dormitories are at increased risk for meningococcal disease. Our aim was to evaluate Greek students planning to study abroad about their level of meningococcal disease awareness and attitudes and practices towards meningococcal vaccination. Methods We studied 231 Greek ERASMUS students using a questionnaire. Results Students had a mean number of 4.1 correct answers out of six questions. In particular 66.5% 79.3%, 72.3% and 82.3% of them answered correctly about the etiology, transmission, epidemiology and treatment of meningococcal disease, respectively. Only 23.4% were vaccinated, whereas 14.7% were planning to do so in the near future. Students who answered correctly ≥5 questions were more likely to be male, vaccinated against meningococcal meningitis and science students. Conclusion We found an overall good level of knowledge about meningococcal disease among Greek students planning to study or already studying abroad. Knowledge about meningococcal disease was associated with vaccine uptake. However, vaccination rate against meningococcal disease was low.

Clinical experience with the meningococcal B vaccine, Bexsero(®): Prospects for reducing the burden of meningococcal serogroup B disease.

PubMed

Watson, Philip S; Turner, David P J

2016-02-10

Although rare, invasive meningococcal disease remains an important cause of mortality and morbidity in children and young adults. Vaccines have been successfully introduced to help protect against meningococcal disease caused by serogroups A, C, W and Y, but until recently, a vaccine for serogroup B (MenB) was not available. In many industrialised countries, MenB causes the majority of meningococcal disease. Moreover, MenB outbreaks occur unpredictably, particularly in high-risk populations, such as university students. In 2013, Bexsero(®) became the first broad-coverage vaccine to be licensed for active immunisation against MenB disease. Bexsero is now licensed in more than 35 countries worldwide for varying age groups, including the EU, Australia, Brazil, Canada, Chile, Uruguay and the USA. Clinical recommendations for the use of Bexsero have been published in several countries. Recommendations include use in high-risk groups, outbreak control and routine infant immunisation. Since initial licensure, considerable clinical experience has been gained. In Canada, 43,740 individuals received Bexsero during a vaccination programme in the Saguenay-Lac-Saint-Jean region of Quebec, where local disease incidence was high. In the USA, Bexsero was administered to >15,000 individuals during two college outbreaks prior to licensure, under an Investigational New Drug protocol. In the UK, the Joint Committee on Vaccination and Immunisation has recommended the inclusion of Bexsero in the routine immunisation schedule for infants. Publically funded vaccination programmes have been initiated in Italy, and there has been widespread use of the vaccine outside of publically reimbursed programmes. Overall, >1,000,000 doses of Bexsero have been distributed in 19 countries worldwide since 2013. The emerging clinical experience with Bexsero is consistent with findings from pre-licensure clinical studies, and no new safety concerns have been identified. Additional data on length of

Safety and immunogenicity of conjugate quadrivalent meningococcal vaccination after hematopoietic cell transplantation

PubMed Central

Pandit, Alisha; Antin, Joseph H.; Walsh, Stephen R.; Huynh, Daisy; Ghobrial, Irene M.; Baden, Lindsey R.; Issa, Nicolas C.

2018-01-01

Immunization with the conjugated quadrivalent (serogroups A, C, Y, and W-135) meningococcal vaccine (MCV4) after hematopoietic cell transplantation (HCT) is recommended. However, immune responses to MCV4 have not been prospectively studied after HCT. We conducted a vaccine response study among 67 adults who received 1 MCV4 dose a year after autologous or allogeneic HCT from January to September 2014. Pre- and postvaccination serogroup serum bactericidal antibody (SBA) titers were measured a median of 57 days after vaccination. Serogroup-specific responses were defined as a fourfold increase in SBA titer with postvaccination titers ≥1:8. Prior to vaccination, 44 (65.7%) patients had no protective titers (<1:8) to any meningococcal serogroup, and 3 (4.5%) patients had protective titers to all 4 serogroups. The median serogroup-specific postvaccination SBA titers were 1:2048 for A, 1:64 for C, 1:128 for W-135, and 1:128 for Y (P < .001 for all pre- and postvaccination pairwise comparisons; similar among serogroups, Spearman ρ 0.5-0.6, P < .0001). Among serogroup-specific nonimmune patients prior to vaccination, serogroup-specific response rates were 76.9%, 65.5%, 51.7%, and 65% to serogroups A, C, W-135, and Y, respectively. One dose of MCV4 elicited protective titers in the majority of patients. These data suggest that a second vaccine dose may be beneficial. PMID:29871892

Complications of serogroup B meningococcal disease in survivors: a review.

PubMed

Dastouri, Fereshteh; Hosseini, Ahmad Mirmohammad; Haworth, Elizabeth; Khandaker, Gulam; Rashid, Harunor; Booy, Robert

2014-01-01

This systematic review evaluates the prevalence of long-term complications of serogroup B meningococcal disease (MD) in light of the recent licensure of a vaccine against meningococcal B disease. Twelve appropriate studies were identified by searching available databases from 1946 to July 2014. The average prevalence of hearing impairment was 4.2% among serogroup B MD survivors; 2.3% suffered amputation and 2.3% developed seizures. When compared with complications due to non-meningococcal B bacterial meningitis, physical impairment and seizures were more common in survivors of meningococcal B disease but hearing impairment had similar prevalence. Few studies quantified less frequent complications such as visual impairment and cognitive dysfunction. Better comprehensive reporting of the complications and costs of serogroup B MD in survivors and their families is needed to inform vaccination policy.

Meningococcal disease. Secondary attack rate and chemoprophylaxis in the United States, 1974.

PubMed

1976-01-19

Three hundred twenty-six reported cases of meningococcal disease in the United States from November 1973 through March 1974 were investigated. Three household members became ill with meningococcal disease following onset of the initial case in their household. The secondary attack rate was approximately 3/1,000 household members. In 60% of the households, members were given an antimicrobial drug as chemoprophylaxis for meningococcal disease, but only 35% received minocycline hydrochloride or rifampin, the two drugs now available for the eradication of sulfonamide-resistant meningococci from the nasopharynx. Only 26% given chemoprophylaxis received the drug within 24 hours after the patient's hospital admission. Survey results indicate that the secondary attack rate of meningococcal disease may justify the use of chemoprophylaxis, but that frequently in the United States, the drugs given are likely to be ineffective, give too late, or administered to persons who are not at high risk to meningococcal disease.

Epidemic meningococcal disease: recommendations for travelers to Nepal.

PubMed

1985-03-08

In the Kathmandu Valley of Nepal, an epidemic of serogroup A meningococcal meningitis resulted in 875 cases and 95 deaths during the 1st 6 months of 1983. The overall annual attack rate was 103 cases/100,000 population; the case fatality ratio was 11%. The highest age-specific attack rate (223/100,000) occurred among children under age 1 year. 3 times as many cases occurred in Kathmandu during December 1983 and January 1984 as in the same period a year previously. A mass vaccination campaign was initiated on February 8, 1984, and 330,000 doses of bivalent A/C meningococcal vaccine were administered, achieving approximately 65% coverage of the target population. A marked decline in the number of meningitis cases occurred coincident with the initiation of the mass campaign. In 1985 meningococcal meningitis is occurring at a much lower rate than in 1984, but meningococcal disease among hikers now is being recognized. Over the January 1984-January 1985 period, 2 culture-confirmed and 4 clinically suspected cases of meningococcal disease were documented among tourists from western countries traveling in Nepal. Patients ranged in age from 16-40 years. 5 patients had evidence of meningococcemia; the other had meningitis alone. 2 patients died, and all became ill during or shortly after hiking outside kathmandu. 3 patients were from the US, 2 from Australia, and 1 from Switzerland. Tables present data on cases of specified notifiable diseases in the US.

Molecular Characterization of Invasive Meningococcal Isolates from Countries in the African Meningitis Belt before Introduction of a Serogroup A Conjugate Vaccine

PubMed Central

Caugant, Dominique A.; Kristiansen, Paul A.; Wang, Xin; Mayer, Leonard W.; Taha, Muhamed-Kheir; Ouédraogo, Rasmata; Kandolo, Denis; Bougoudogo, Flabou; Sow, Samba; Bonte, Laurence

2012-01-01

Background The serogroup A conjugate meningococcal vaccine, MenAfriVac, was introduced in mass vaccination campaigns in December 2010 in Burkina Faso, Mali and Niger. In the coming years, vaccination will be extended to other African countries at risk of epidemics. To document the molecular characteristics of disease-causing meningococcal strains circulating in the meningitis belt of Africa before vaccine introduction, the World Health Organization Collaborating Centers on Meningococci in Europe and United States established a common strain collection of 773 isolates from cases of invasive meningococcal disease collected between 2004 and 2010 from 13 sub-Saharan countries. Methodology All isolates were characterized by multilocus sequence typing, and 487 (62%) were also analyzed for genetic variation in the surface antigens PorA and FetA. Antibiotic susceptibility was tested for part of the collection. Principal Findings Only 19 sequence types (STs) belonging to 6 clonal complexes were revealed. ST-5 clonal complex dominated with 578 (74.8%) isolates. All ST-5 complex isolates were remarkably homogeneous in their PorA (P1.20,9) and FetA (F3-1) and characterized the serogroup A strains which have been responsible for most epidemics during this time period. Sixty-eight (8.8%) of the 773 isolates belonged to the ST-11 clonal complex which was mainly represented by serogroup W135, while an additional 38 (4.9%) W135 isolates belonged to the ST-175 complex. Forty-eight (6.2%) serogroup X isolates from West Africa belonged to the ST-181 complex, while serogroup X cases in Kenya and Uganda were caused by an unrelated clone, ST-5403. Serogroup X, ST-181, emerged in Burkina Faso before vaccine introduction. Conclusions In the seven years preceding introduction of a new serogroup A conjugate vaccine, serogroup A of the ST-5 clonal complex was identified as the predominant disease-causing strain. PMID:23029368

Global practices of meningococcal vaccine use and impact on invasive disease

PubMed Central

Ali, Asad; Jafri, Rabab Zehra; Messonnier, Nancy; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar; Abramson, Jon

2014-01-01

A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs. PMID:24548156

Psychiatric Adjustment in the Year after Meningococcal Disease in Childhood

ERIC Educational Resources Information Center

Shears, Daniel; Nadel, Simon; Gledhill, Julia; Gordon, Fabiana; Garralda, M. Elena

2007-01-01

Objective: To assess psychiatric status after meningococcal disease. Method: Cohort study of 66 children (34 boys, 32 girls) ages 4 to 17 years admitted to pediatric hospitals with meningococcal disease. The main outcome measure was psychiatric disorder (1-year period and point prevalence on the Schedule for Affective Disorders and Schizophrenia…

Cost-effectiveness of conjugate meningococcal vaccination strategies in the United States.

PubMed

Shepard, Colin W; Ortega-Sanchez, Ismael R; Scott, R Douglas; Rosenstein, Nancy E

2005-05-01

The US Food and Drug Administration approved a meningococcal conjugate A/C/Y/W-135 vaccine (MCV-4) for use in persons aged 11 to 55 years in January, 2005; licensure for use in younger age groups is expected in 2 to 4 years. To evaluate and compare the projected health and economic impact of MCV-4 vaccination of US adolescents, toddlers, and infants. Cost-effectiveness analysis from a societal perspective based on data from Active Bacterial Core Surveillance (ABCs) and other published and unpublished sources. Sensitivity analyses in which key input measures were varied over plausible ranges were performed. A hypothetical 2003 US population cohort of children 11 years of age and a 2003 US birth cohort. Hypothetical routine vaccination of adolescents (1 dose at 11 years of age), toddlers (1 dose at 1 year of age), and infants (3 doses at 2, 4, and 6 months of age). Each vaccination scenario was compared with a "no-vaccination" scenario. Meningococcal cases and deaths prevented, cost per case prevented, cost per life-year saved, and cost per quality-adjusted life-year saved. Routine MCV-4 vaccination of US adolescents (11 years of age) would prevent 270 meningococcal cases and 36 deaths in the vaccinated cohort over 22 years, a decrease of 46% in the expected burden of disease. Before program costs are counted, adolescent vaccination would reduce direct disease costs by $18 million and decrease productivity losses by $50 million. At a cost per vaccination (average public-private price per dose plus administration fees) of $82.50, adolescent vaccination would cost society $633000 per meningococcal case prevented and $121000 per life-year saved. Key variables influencing results were disease incidence, case-fatality ratio, and cost per vaccination. The cost-effectiveness of toddler vaccination is essentially equivalent to adolescent vaccination, whereas infant vaccination would be much less cost-effective. Routine MCV-4 vaccination of US children would reduce the burden

Arthritis secondary to meningococcal disease: A case series of 7 patients.

PubMed

Masson-Behar, Vanina; Jacquier, Hervé; Richette, Pascal; Ziza, Jean-Marc; Zeller, Valérie; Rioux, Christophe; Coustet, Baptiste; Dieudé, Philippe; Ottaviani, Sébastien

2017-07-01

Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported.This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection.We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture.A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications.Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.

Epidemiology of infant meningococcal disease in the United States, 2006-2012.

PubMed

MacNeil, Jessica R; Bennett, Nancy; Farley, Monica M; Harrison, Lee H; Lynfield, Ruth; Nichols, Megin; Petit, Sue; Reingold, Arthur; Schaffner, William; Thomas, Ann; Pondo, Tracy; Mayer, Leonard W; Clark, Thomas A; Cohn, Amanda C

2015-02-01

The incidence of meningococcal disease is currently at historic lows in the United States; however, incidence remains highest among infants aged <1 year. With routine use of Haemophilus influenzae type b and pneumococcal vaccines in infants and children in the United States, Neisseria meningitidis remains an important cause of bacterial meningitis in young children. Data were collected from active, population- and laboratory-based surveillance for N meningitidis conducted through Active Bacterial Core surveillance during 2006 through 2012. Expanded data collection forms were completed for infant cases identified in the surveillance area during 2006 through 2010. An estimated 113 cases of culture-confirmed meningococcal disease occurred annually among infants aged <1 year in the United States from 2006 through 2012, for an overall incidence of 2.74 per 100,000 infants. Among these cases, an estimated 6 deaths occurred. Serogroup B was responsible for 64%, serogroup C for 12%, and serogroup Y for 16% of infant cases. Based on the expanded data collection forms, a high proportion of infant cases (36/58, 62%) had a smoker in the household and the socioeconomic status of the census tracts where infant meningococcal cases resided was lower compared with the other Active Bacterial Core surveillance areas and the United States as a whole. The burden of meningococcal disease remains highest in young infants and serogroup B predominates. Vaccines that provide long-term protection early in life have the potential to reduce the burden of meningococcal disease, especially if they provide protection against serogroup B meningococcal disease. Copyright © 2015 by the American Academy of Pediatrics.

Meningococcal disease in catalonia 1 year after mass vaccination campaign with meningococcal group C polysaccharide vaccine.

PubMed

Cardeñosa, N; Domínguez, A; Martínez, A; Alvarez, J; Pañella, H; Godoy, P; Minguell, S; Camps, N; Vázquez, J A

2003-12-01

The aim of this study was to investigate the clinical and epidemiological characteristics of meningococcal disease in Catalonia (Spain) after vaccination with the polysaccharide vaccine. Cases were collected by the Statutory Diseases Reporting System. 176 cases were reported, an overall incidence of 2.9/100,000 persons/year. 60% of cases occurred during winter and spring. The case fatality rate was 6.3%. The highest age incidence was in children under 2 years of age (48/100,000 persons/year). Comparison of the cases detected by the Statutory Diseases Reporting System with those obtained by the Microbiological Reporting System shows that meningococcal disease surveillance in Catalonia was relatively complete (95.7%), with a positive predictive value of 66.3%. 115 cases (65%) were culture-confirmed with a rate of 1.9/100,000 persons/year. 86 (75%) cases were due to Neisseria meningitidis serogroup B and 21 to serogroup C (18%). Although infections due to serogroup C have decreased after mass vaccination with the polysaccharide vaccine, it is likely that the number of infections will decrease further with the conjugate meningococcal group C vaccine.

Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

PubMed

Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

2010-01-01

With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

Long-term immunogenicity and safety after a single dose of the quadrivalent meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine in adolescents and adults: 5-year follow-up of an open, randomized trial.

PubMed

Borja-Tabora, Charissa Fay Corazon; Montalban, Cecilia; Memish, Ziad A; Boutriau, Dominique; Kolhe, Devayani; Miller, Jacqueline M; Van der Wielen, Marie

2015-10-06

Long-term protection against meningococcal disease is associated with persistence of post-vaccination antibodies at protective levels. We evaluated the bactericidal antibody persistence and safety of the quadrivalent meningococcal serogroups A, C, W and Y tetanus-toxoid conjugate vaccine (MenACWY-TT) and the meningococcal polysaccharide serogroups A, C, W, and Y vaccine (MenACWY-PS) up to 5 years post-vaccination. This phase IIb, open, randomized, controlled study conducted in the Philippines and Saudi Arabia consisted of a vaccination phase and a long-term persistence phase. Healthy adolescents and adults aged 11-55 years were randomized (3:1) to receive a single dose of MenACWY-TT (ACWY-TT group) or MenACWY-PS (Men-PS group). Primary and persistence results up to 3 years post-vaccination have been previously reported. Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA, cut-off titers 1:8 and 1:128) at Year 4 and Year 5 post-vaccination. Vaccine-related serious adverse events (SAEs) and cases of meningococcal disease were assessed up to Year 5. Of the 500 vaccinated participants, 404 returned for the Year 5 study visit (Total Cohort Year 5). For the Total Cohort Year 5, 71.6-90.0 and 64.9-86.3 % of MenACWY-TT recipients had rSBA titers ≥1:8 and ≥1:128, respectively, compared to 24.8-74.3 and 21.0-68.6 % of MenACWY-PS recipients. The rSBA geometric mean titers (GMTs) remained above the pre-vaccination levels in both treatment groups. Exploratory analyses suggested that both rSBA GMTs as well as the percentages of participants with rSBA titers above the cut-offs were higher in the ACWY-TT than in the Men-PS group for serogroups A, W and Y, with no apparent difference for MenC. No SAEs related to vaccination or cases of meningococcal disease were reported up to Year 5. These results suggest that a single dose of MenACWY-TT could protect at least 72 % of vaccinated

Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England

PubMed Central

Giuliani, Marzia Monica; Biolchi, Alessia; Pizza, Mariagrazia; Beebeejaun, Kazim; Lucidarme, Jay; Findlow, Jamie; Ramsay, Mary E.; Borrow, Ray

2016-01-01

Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain. PMID:26811872

Meningococcal disease, a clinical and epidemiological review.

PubMed

Batista, Rodrigo Siqueira; Gomes, Andréia Patrícia; Dutra Gazineo, Jorge Luiz; Balbino Miguel, Paulo Sérgio; Santana, Luiz Alberto; Oliveira, Lisa; Geller, Mauro

2017-11-01

Meningococcal disease is the acute infection caused by Neisseria meningitidis, which has humans as the only natural host. The disease is widespread around the globe and is known for its epidemical potential and high rates of lethality and morbidity. The highest number of cases of the disease is registered in the semi-arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional outbreaks, epidemics and sporadic cases occurring throughout the year, especially in the winter. The major epidemics of the disease occurred in Brazil in the 70's caused by serogroups A and C. Serogroups B, C and Y represent the majority of cases in Europe, the Americas and Australia. However, there has been a growing increase in serogroup W in some areas. The pathogen transmission happens for respiratory route (droplets) and clinically can lead to meningitis and sepsis (meningococcemia). The treatment is made with antimicrobial and supportive care. For successful prevention, we have some measures like vaccination, chemoprophylaxis and droplets' precautions. In this review, we have described and clarify clinical features of the disease caused by N. meningitidis regarding its relevance for healthcare professionals. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Meningococcal disease in South African goldmines--epidemiology and strategies for control.

PubMed

Sonnenberg, P; Silber, E; Ho, K C; Koornhof, H J

2000-05-01

To describe the epidemiology of meningococcal disease in South African goldmines and to suggest strategies for the prevention and control of further outbreaks. We prospectively investigated a meningococcal outbreak that occurred in 1996 and describe the control measures that were implemented. In addition, we conducted a retrospective analysis of routinely collected data on meningococcal disease in these mines from 1972 to 1996. Four goldmines in Gauteng, employing 30,000 workers who live in hostels. All cases of meningococcal disease at the mine hospital. Between 1972 and 1976, 588 cases were diagnosed, with peaks in 1972 (203 cases, 727/100,000) and 1975 (147 cases, 564/100,000). Since 1978 less than 5 cases have been reported in most years, but smaller outbreaks occurred in 1990 (30 cases, 89/100,000) and 1996 (14 cases, 50/100,000). The 1996 outbreak (group A, clone I-1) was part of a larger outbreak in Gauteng that originated in Mozambique and began in one mine in July 1996, after which a mass vaccination campaign was implemented. This was followed by a smaller outbreak among non-vaccinated workers at an adjacent mine. Five patients were new recruits. Despite a dramatic reduction in meningococcal disease over the last 25 years due mainly to changes in the work force, there are still outbreaks in this community. Those most at risk are young men who are new to the industry. Suggestions for prevention include effective surveillance, routine vaccination of new recruits and a rapid response to outbreaks, with mass vaccination and provision of chemoprophylaxis to close contacts.

Meningococcal conjugate vaccines: optimizing global impact

PubMed Central

Terranella, Andrew; Cohn, Amanda; Clark, Thomas

2011-01-01

Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. PMID:22114508

52 Loop-mediated isothermal amplification PCR (LAMP) for the rapid identification of invasive meningococcal disease in the emergency department.

PubMed

Waterfield, Thomas; Patenall, Bethany; McKenna, James; Fairley, Derek

2017-12-01

Despite successful vaccination programmes meningococcal disease (MD) remains the leading infectious cause of septicaemia and death in children in the UK and Ireland. 1,2 The early diagnosis of MD significantly improves outcomes with reduced morbidity and mortality. 1,2 The early stages of MD are often indistinguishable from a simple viral illness making an early positive diagnosis of MD difficult. 1 Hibergene have developed a commercially available bedside Loop-mediated isothermal AMPlification PCR (LAMP-MD) test that is a highly sensitive 0.89 (95%CI 0.72-0.96) and specific 1.0 (95%CI 0.97-1.0) for identifying children with invasive MD (4) (figure 1).emermed;34/12/A895-a/F1F1F1Figure 1 AIMS: The aims of this RCEM funded study were:Assess the ease of use and suitability for the EDDetermine the time taken to perform the testIndependently verify LAMP-MD performance against TaqMan quantitative PCR. The LAMP-MD was assessed for practicality and ease of use within the ED including an assessment of training needs, footprint and health and safety requirements.For verification of the Hibergene LAMP-MD analyser and assay we used dry nasopharyngeal swabs sent for viral screening. Additional verification was undertaken using N. meningitidis genomic DNA spiked over a range of concentrations. This included serotypes A, B, C, W, X and Y and a dilution series to determine the limit of detection. All samples were then analysed using real time TaqMan qPCR. The LAMP-MD analyser was easy to use and could be accommodated in the EDThe mean time for detection of Meningococcal DNA was 14.01 minDetection of meningococcal serogroups A, B, C, W, X and Z was confirmedThe detection limit for dry nasopharyngeal swabs was below 2 genomic copies per µlNo non-specific amplification was observed in 17 randomly selected negative clinical swabsThe LAMP-MD assay was 100% sensitive and specific relative to real-time TaqMAN PCR. LAMP-MD is a practical, rapid point of care test that can reliably

[Clinical features and prognostic factors of meningococcal disease: a case series study in Chile during the 2012-2013 outbreak].

PubMed

Matute, Isabel; Olea, Andrea; López, Darío; Loayza, Sergio; Nájera, Manuel; González, Claudia; Poffald, Lucy; Hirmas, Macarena; Delgado, Iris; Pedroni, Elena; Alfaro, Tania; Gormaz, Ana María; Sanhueza, Gabriel; Vial, Pablo; Dabanch, Jeannette; Gallegos, Doris; Aguilera, Ximena

2015-10-01

Meningococcal disease (MD) is a major global problem because of its case fatality rate and sequels. Since 2012 cases of serogroup W have increased in Chile, with nonspecific clinical presentation, high case fatality rate and serious consequences. To characterize the evolution and outcome of MD cases between January 2012 and March 2013 in Chile. Case series considering 149 MD cases of 7 regions. A questionnaire was applied and clinical records were reviewed, including individual, agent, clinical course and healthcare process variables. The analysis allowed to obtain estimates of the OR as likelihood of dying. 51.5% was meningococcemia, the case fatality rate reached 27%, prevailing serogroup W (46.6%). Factors that increased the probability of dying: > age, belonging to indigenous people, having lived a stressful event, having diarrhea, impaired consciousness, cardiovascular symptoms, low oxygen saturation and low Glasgow coma scale score. The case fatality rate exceeded normal levels and was higher in serogroup W. Increasing in this serogroup, associated to the increased presence of nonspecific symptoms or rapid progression to septicemia, hit a health system accustomed to more classic meningococcal disease presentation, which could partly explain the observed increased fatality rate.

Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

PubMed

Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J

2013-07-01

Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

Meningococcal vaccine development--from glycoconjugates against MenACWY to proteins against MenB--potential for broad protection against meningococcal disease.

PubMed

Dull, Peter M; McIntosh, E David

2012-05-30

Novartis Vaccines has a long-standing research and development interest in the prevention of invasive meningococcal disease. From the initial licensure of the monovalent meningococcal C glycoconjugate vaccine, Menjugate(®), in response to the emergence of a virulent serogroup C ST-11 strain in the United Kingdom to the more recent development and licensure of a quadrivalent meningococcal ACWY glycoconjugate vaccine, Menveo(®), Novartis has a continuing commitment to the development of more effective tools for the control of meningococcal disease. Menveo is now licensed for use in adolescents and adults in over 50 countries and results from phase III studies have shown the vaccine to be well-tolerated and highly immunogenic in infants with vaccination beginning from 2 months of age. The 'holy grail' of meningococcal disease control is a broadly protective vaccine against serogroup B (MenB), preferably a vaccine that protects all age groups including infants. As the serogroup B capsule is poorly immunogenic, efforts over the past 40 years have focused on identifying conserved proteins expressed on the bacterial surface that elicit bactericidal antibodies. Novartis has approached this problem utilizing genomic tools to identify proteins meeting these criteria in a process now known as 'reverse vaccinology'[1]. This process has resulted in a novel multicomponent MenB vaccine (4CMenB) that consists of four major immunogenic components (three subcapsular MenB protein antigens plus outer membrane vesicles (OMVs) which themselves provide multiple subcapsular antigens, the immunodominant one being PorA). These all induce bactericidal antibodies against the antigens that are important in determining the survival, function, and virulence of the meningococci. Phase II studies of 4CMenB have been completed and have demonstrated that the vaccine is highly immunogenic against reference meningococcal strains selected to support licensure. Post-vaccination sera from clinical

Outer membrane vesicles extracted from Neisseria meningitidis serogroup X for prevention of meningococcal disease in Africa.

PubMed

Acevedo, Reinaldo; Zayas, Caridad; Norheim, Gunnstein; Fernández, Sonsire; Cedré, Barbara; Aranguren, Yisabel; Cuello, Maribel; Rodriguez, Yaimara; González, Humberto; Mandiarote, Aleida; Pérez, Marylin; Hernández, Maritza; Hernández-Cedeño, Mabel; González, Domingo; Brorson, Sverre-Henning; Rosenqvist, Einar; Naess, Lisbeth; Tunheim, Gro; Cardoso, Daniel; García, Luis

2017-07-01

Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N. meningitidis. However, numerous cases of meningitis caused by serogroup X N. meningitidis (MenX) have recently been reported in several African countries. Currently, there are no licensed vaccines against this pathogen and most of the MenX cases have been caused by meningococci from clonal complex (c.c) 181. Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have previously shown to be safe and effective against epidemics of serogroup B meningococcal disease in all age groups. The aim of this work is therefore to obtain, characterize and evaluate the vaccine potential of dOMVs derived from a MenX strain (OMVx). Three experimental lots of OMVx were prepared by deoxycholate extraction from the MenX strain BF 2/97. Size and morphology of the vesicles was determined by Dynamic Light Scattering and electron microscopy, whereas the antigenic composition was characterized by gel electrophoresis and immunoblotting. OMVx were thereafter adsorbed to aluminium hydroxide (OMVx/AL) and two doses of OMVx were administered s.c. to groups of Balb/c mice three weeks apart. The immunogenicity and functional antibody activities in sera were evaluated by ELISA (anti-OMVx specific IgG responses) and serum bactericidal activity (SBA) assay. The size range of OMVx was shown to be between 90 and 120nm, whereas some of the antigens detected were the outer membrane proteins PorA, OpcA and RmpM. The OMVx/AL elicited high anti-OMVx antibody responses with bactericidal activity and no bactericidal activity was observed in the control group of no immunised mice. The results demonstrate that OMVx are immunogenic and could form part of a future vaccine to prevent the majority of meningococcal disease in the African meningitis belt. Copyright © 2017 Elsevier Ltd. All rights reserved.

2010 FIFA world cup South Africa: travel health issues and new options for protection against meningococcal disease.

PubMed

Zuckerman, Jane N; Bröker, Michael; Worth, Christopher

2010-03-01

The public health implications of large crowds gathering at a range of key global events should never be underestimated. This is especially the case with the upcoming 2010 FIFA World Cup South Africa programme where thousands of local and travelling spectators, players and officials from all over the world will be present. Although meningococcal disease contracted whilst actually travelling is relatively rare, any travel health risk assessment should involve consideration of potential exposure to and transmission of this disease where crowding occurs. In South Africa, for reasons not completely understood, the incidence of meningococcal disease is higher than in most European countries. Whilst the currently available polysaccharide vaccines can help protect travellers against meningococcal disease there are some well recognised limitations of such vaccines. These can, however, be overcome with the use of newly developed conjugated quadrivalent meningococcal vaccines. A quadrivalent conjugate vaccine should be the first choice for travellers to areas in which the risk of exposure to meningococcal disease is significant. The conjugated quadrivalent meningococcal vaccine should be recommended for all those attending or playing in the 2010 FIFA World Cup South Africa as well as similar global and regional events.

Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

PubMed

Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

2013-12-09

Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt. Copyright © 2013 Elsevier Ltd. All rights reserved.

Global epidemiology of invasive meningococcal disease

PubMed Central

2013-01-01

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made. PMID:24016339

Global epidemiology of invasive meningococcal disease.

PubMed

Jafri, Rabab Z; Ali, Asad; Messonnier, Nancy E; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar A; Abramson, Jon

2013-09-10

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

Pros and cons of vaccination against serogroup B meningococcal disease.

PubMed

Delgado Rodríguez, Miguel; Domínguez García, Ángela

2018-02-09

A vaccine has recently been approved in the EU against meningococcal serogroup B, the main cause of meningococcal disease. There is a fierce debate about the decision regarding a universal vaccination in infants older than 2 months, as recommended by the majority of scientific societies. In western Europe the only country to have included the universal vaccination is the United Kingdom, with a lower incidence of the disease than Ireland. Other countries have also adopted it, such as the Czech Republic, Cuba and certain regions of Italy. Numerous cost-effectiveness studies have been published regarding the vaccination with different assumptions, which have supported the decision not to implant the universal vaccination because it exceeds the will to pay for a health benefit. We discuss the pros and cons of the universal vaccination against meningococcal B, recommended by the Sociedad Española de Pediatría (Spanish Society of Paediatrics), which as yet has not been implemented. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Pre-admission antibiotics for suspected cases of meningococcal disease.

PubMed

Sudarsanam, Thambu D; Rupali, Priscilla; Tharyan, Prathap; Abraham, Ooriapadickal Cherian; Thomas, Kurien

2013-08-02

Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure and morbidity in people suspected of meningococcal disease. We updated searches of CENTRAL (2013, Issue 4), MEDLINE (1966 to April week 4, 2013), EMBASE (1980 to May 2013), Web of Science (1985 to May 2013), CAB Abstracts (1985 to May 2013), LILACS (1982 to May 2013) and prospective trials registries to May 2013. Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial so data synthesis was not performed. We assessed the overall quality of the evidence using the GRADE approach. We found no RCTs that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label, non-inferiority RCT, conducted during an epidemic in Niger, evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.2, 95% CI 0.6 to 2.6; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.8, 95% CI 0.3 to 2.2; N = 477, 18 clinical failures; moderate-quality evidence) or neurological sequelae (RR 1.3, 95% CI 0.6 to 2.6; N

[Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012].

PubMed

Araya, Pamela; Díaz, Janepsy; Seoane, Mabel; Fernández, Jorge; Terrazas, Solana; Canals, Andrea; Vaquero, Alejandra; Barra, Gisselle; Hormazábal, Juan C; Pidal, Paola; Valenzuela, M Teresa

2014-08-01

Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. To show the results of this surveillance from 2006 to 2012. A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

Awareness of Meningococcal Disease among Travelers from the United Kingdom to the Meningitis Belt in Africa

PubMed Central

Goodman, Anna L.; Masuet-Aumatell, Cristina; Halbert, Jay; Zuckerman, Jane N.

2014-01-01

Meningococcal disease causes considerable morbidity and has a high case-fatality rate. In the United Kingdom, the meningococcal quadrivalent vaccine is recommended for travelers visiting the meningitis belt of Africa. We analyzed 302 responses to a cross-sectional study conducted in 2010 of travelers who had visited the meningitis belt recently or were shortly due to travel there. Using the results of an online questionnaire, we assessed knowledge and understanding of meningococcal disease and likelihood of uptake of meningococcal immunization before travel. Meningococcal vaccine uptake was 30.1%. Although global scores in the questionnaire did not correlate with vaccine uptake, knowledge of the meningitis belt and knowledge of certain key symptoms or signs were statistically associated with high vaccine uptake. We conclude that improved education of travelers may improve vaccine uptake before travel to the meningitis belt in Africa. PMID:24891461

Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease.

PubMed

Domingo, Pere; Muñiz-Diaz, Eduardo; Baraldès, Maria A; Arilla, Marina; Barquet, Nicolau; Pericas, Roser; Juárez, Cándido; Madoz, Pedro; Vázquez, Guillermo

2002-01-01

In vitro studies have shown that the neutrophil Fc gamma receptor IIA (FcgammaRIIA) polymorphism influences the phagocytic capacity of neutrophils and the removal of encapsulated bacteria from the bloodstream. In particular, the R/R131 allotype is associated with less phagocytic activity. We performed a case-control study to determine the influence of the FcgammaRIIA polymorphism (R/R131, R/H131, H/H131) on the risk and outcome of meningococcal disease. The polymorphisms were measured in 130 patients with microbiologically proven meningococcal disease diagnosed from 1987 to 1998 (cases) and 260 asymptomatic sex-matched blood donors (controls). Clinical manifestations and complications of meningococcal disease were recorded, and a prognostic score (based on age, hemorrhagic diathesis, neurologic signs, and the absence of preadmission antibiotic) therapy was calculated. The distributions of FcgammaRIIA allotypes were similar in cases and controls. However, among patients with meningococcal infection, fulminant meningococcal disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.0 to 16; P = 0.04) and meningococcemia without meningitis (OR = 3.0; 95% CI: 1.4 to 7.8; P = 0.004) were more common in those with the FcgammaRIIA-R/R131 allotype. Complications were also significantly more frequent in these patients. Of the 42 patients with the R/R131 allotype, 31 (74%) had an adverse prognostic score, compared with 7% (4 of 59) of those with the R/H131 allotype and 3% (1 of 29) of those with the H/H131 allotype (P <0.0001). The FcgammaRIIA-R/R131 allotype is associated with more severe forms of meningococcal disease.

Meningococcal disease: recognition, treatment, and prevention.

PubMed

Herf, C; Nichols, J; Fruh, S; Holloway, B; Anderson, C U

1998-08-01

Meningococcal disease is an infection caused by Neisseria meningitidis, a gram-negative diplococcus that is the leading cause of bacterial meningitis in children and young adults in the United States, with an estimated 2,600 cases reported each year. N. meningitidis infection rates are highest in children 3 to 12 months of age. Four distinct clinical situations are associated with meningococcal infection. The most common is asymptomatic nasopharyngeal colonization. Benign bacteremia is discovered in the absence of classical clinical findings of meningococcemia, but blood cultures are positive for N. meningitidis. Meningitis, the most common pathologic presentation, is associated with fever, headache, and nuchal rigidity. The mortality rate is about 5% in children and 10% to 15% in adults. Meningococcemia, the most severe form of infection, may involve petechial rash, hypotension, and disseminated intravascular coagulation. It is a fulminant condition that can, if untreated, progress from initial symptoms to coma and death in 12 to 48 hours. Spread of these endemic cases can be controlled by administering prophylactic antibiotics to close contacts of patients.

Pre-admission antibiotics for suspected cases of meningococcal disease.

PubMed

Sudarsanam, Thambu D; Rupali, Priscilla; Tharyan, Prathap; Abraham, Ooriapadickal Cherian; Thomas, Kurien

2017-06-14

Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease. We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017. Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach. We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to

Meningococcal Disease (Bacterial Meningitis) Vaccine and Pregnancy

MedlinePlus

... brand names include Menveo® and Menactra®) and meningococcal polysaccharide vaccine or MPSV4 for short (brand name: Menomune®). ... Adam I and Abdalla MA. 2005. Is meningococcal polysaccharide vaccine safe during pregnancy? Ann Trop Med Parasitol ...

The case-fatality rate of meningococcal disease in Catalonia, 1990-1997.

PubMed

Domínguez, Angela; Cardeñosa, Neus; Pañella, Helena; Orcau, Angels; Companys, Maria; Alseda, Miquel; Oviedo, Manuel; Carmona, Glòria; Minguell, Sofia; Salleras, Lluis

2004-01-01

The objective was to analyse the case-fatality rate (CFR) of meningococcal disease (MD) in Catalonia, Spain. A retrospective study was carried out. Clinical histories of cases of MD reported for the period 1990-1997 in Catalonia were reviewed. For all cases, the variables gender, age, clinical type, y of presentation, province, phenotype and death by meningococcal disease were collected. The association between death and the other variables was studied by bivariate and unconditional logistic regression analysis. In the 2343 cases studied there were 146 deaths (6.2%) due to meningococcal disease. The CFR was higher in females (OR: 1.5, 95%CI: 1.1-2.1), in the 20 to 49 y (OR: 2.4, 95%CI: 1.2-4.9) and > or = 50 y (OR: 5.3, 95%CI: 2.8-10.1) age groups, in cases with septicaemia (OR: 2.4, 95%CI: 1.6-3.5), in the cases produced by serogroup A (OR: 4.7, 95%CI: 1.0-23.4) and in cases occurring during 1993 (OR: 2.1, 95%CI: 1.1-4.1) or in the province of Lleida (OR: 2.9, 95%CI: 1.2-7.2). In the multivariate analysis, death was associated with the 20-49 y age group (OR: 3.9, 95%CI: 1.8-8.4), the > or = 50 y age group (OR: 7.3, 95%CI: 3.6-14.7), septicaemia (OR: 3.1; 95%CI: 2.0-4.7) and residing in the province of Lleida (OR: 3.2; 95%CI: 1.2-8.5). The CFR of meningococcal disease in Catalonia was not associated with the emergent phenotype C:2b:P1.2,5 strain, which caused an outbreak in other regions of Spain.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease.

PubMed

Granoff, Dan M

2009-06-24

Killing of Neisseria meningitidis can result from complement-mediated serum bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers > or =1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers > or =1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

PubMed Central

Granoff, Dan M.

2009-01-01

Killing of Neisseria meningitidis can result from complement-mediated bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers ≥1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers ≥1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease. PMID:19477054

Using a point-of-dispensing clinic for prophylaxis of meningococcal disease.

PubMed

Ngo, Van P; Civen, Rachel H; Dassey, David E; Davenport, Deborah; Mascola, Laurene

2010-03-01

A point-of-dispensing clinic was held to distribute ciprofloxacin prophylaxis when 2 high school students were reported to the health department with invasive meningococcal disease. Of more than 3,100 school staff and students in attendance, 2,861 received prophylaxis. A survey was administered to students 2 weeks postclinic to better understand the motivations for clinic attendance and to quantify side effects of oral 500-mg ciprofloxacin prophylaxis. Data collected included reasons for attendance and perception of risk for acquiring meningococcal disease, rated on a 1-to-5 scale; type of contact with cases; and side effects. Of 2,888 students, 1,624 completed surveys; 1,390 took ciprofloxacin. The students rated parental influence and directives from the high school as reasons for attendance a mean of 3.97 and 3.34, respectively. The mean rating for risk of acquiring meningococcal disease was 1.49. Only 3% reported direct contact with case(s). Side effects, most commonly headache (17%) and stomachache (10%), were reported in 40% of students. Serious side effects such as rash and facial swelling were reported in <1%. In this adolescent population, few serious side effects and no joint disorders were reported after they ingested single-dose ciprofloxacin; however, many received the prophylaxis unnecessarily. Students were motivated by parents and school officials. Health departments should collaborate with schools to prepare and disseminate messages that balance the risks of unnecessary antibiotic use with those of exposure to disease.

Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis

PubMed Central

Mustapha, Mustapha M.; Marsh, Jane W.; Krauland, Mary G.; Fernandez, Jorge O.; de Lemos, Ana Paula S.; Dunning Hotopp, Julie C.; Wang, Xin; Mayer, Leonard W.; Lawrence, Jeffrey G.; Hiller, N. Luisa; Harrison, Lee H.

2015-01-01

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution. PMID:26629539

Meningococcal Carriage Following a Vaccination Campaign With MenB-4C and MenB-FHbp in Response to a University Serogroup B Meningococcal Disease Outbreak-Oregon, 2015-2016.

PubMed

McNamara, Lucy A; Thomas, Jennifer Dolan; MacNeil, Jessica; Chang, How Yi; Day, Michael; Fisher, Emily; Martin, Stacey; Poissant, Tasha; Schmink, Susanna E; Steward-Clark, Evelene; Jenkins, Laurel T; Wang, Xin; Acosta, Anna

2017-11-27

Limited data exist on the impact of the serogroup B meningococcal (MenB) vaccines MenB-FHbp and MenB-4C on meningococcal carriage and herd protection. We therefore assessed meningococcal carriage following a MenB vaccination campaign in response to a university serogroup B meningococcal disease outbreak in 2015. A convenience sample of students recommended for vaccination provided oropharyngeal swab specimens and completed questionnaires during 4 carriage surveys over 11 months. Isolates were tested by real-time polymerase chain reaction analysis, slide agglutination, and whole-genome sequencing. Vaccination history was verified via university records and the state immunization registry. A total of 4225 oropharyngeal swab specimens from 3802 unique participants were analyzed. Total meningococcal and genotypically serogroup B carriage prevalence among sampled students were stable, at 11%-17% and 1.2%-2.4% during each round, respectively; no participants carried the outbreak strain. Neither 1-3 doses of MenB-FHbp nor 1-2 doses of MenB-4C was associated with decreased total or serogroup B carriage prevalence. While few participants completed the full MenB vaccination series, limiting analytic power, these data suggest that MenB-FHbp and MenB-4C do not have a large, rapid impact on meningococcal carriage and are unlikely to provide herd protection in the context of an outbreak response. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information.

PubMed

Granier, S; Owen, P; Pill, R; Jacobson, L

1998-01-24

To describe the presentation of meningococcal disease in primary care; to explore how general practitioners process clinical and contextual information in children with meningococcal disease; and to describe how this information affects management. Qualitative analysis of semistructured interviews. General practices in South Glamorgan. 26 general practitioners who between January 1994 and December 1996 admitted 31 children (under 16 years of age) in whom meningococcal disease was diagnosed. Categories of clinical rules and techniques used by general practitioners in processing each case. 22 children had rashes; in 16 of them the rashes were non-blanching. When present, a haemorrhagic rash was the most important factor in the doctor's decision to admit a child. 22 children had clinical features not normally expected in children with acute self limiting illnesses--for example, lethargy, poor eye contact, altered mental states, pallor with a high temperature, and an abnormal cry. Contextual information, such as knowledge of parents' consultation patterns and their normal degree of anxiety, played an important part in the management decisions in 15 cases. Use of penicillin was associated with the certainty of diagnosis and the presence and type of haemorrhagic rash. The key clinical feature of meningococcal disease--a haemorrhagic rash--was present in only half of the study children. The general practitioners specifically hunted for the rash in some ill children, but doctors should not be deterred from diagnosing meningococcal disease and starting antibiotic treatment if the child is otherwise well, if the rash has an unusual or scanty distribution, or if the rash is non-haemorrhagic.

Strains Responsible for Invasive Meningococcal Disease in Patients With Terminal Complement Pathway Deficiencies.

PubMed

Rosain, Jérémie; Hong, Eva; Fieschi, Claire; Martins, Paula Vieira; El Sissy, Carine; Deghmane, Ala-Eddine; Ouachée, Marie; Thomas, Caroline; Launay, David; de Pontual, Loïc; Suarez, Felipe; Moshous, Despina; Picard, Capucine; Taha, Muhamed-Kheir; Frémeaux-Bacchi, Véronique

2017-04-15

Patients with terminal complement pathway deficiency (TPD) are susceptible to recurrent invasive meningococcal disease (IMD). Neisseria meningitidis (Nm) strains infecting these patients are poorly documented in the literature. We identified patients with TPD and available Nm strains isolated during IMD. We investigated the genetic basis of the different TPDs and the characteristics of the Nm strains. We included 56 patients with C5 (n = 8), C6 (n = 20), C7 (n = 18), C8 (n = 9), or C9 (n = 1) deficiency. Genetic study was performed in 47 patients and 30 pathogenic variants were identified in the genes coding for C5 (n = 4), C6 (n = 5), C7 (n = 12), C8 (n = 7), and C9 (n = 2). We characterized 61 Nm strains responsible for IMD in the 56 patients with TPD. The most frequent strains belonged to groups Y (n = 27 [44%]), B (n = 18 [30%]), and W (n = 8 [13%]). Hyperinvasive clonal complexes (CC11, CC32, CC41/44, and CC269) were responsible for 21% of IMD cases. The CC23 predominates and represented 26% of all invasive isolates. Eleven of the 15 clonal complexes identified fit to 12 different clonal complexes belonging to carriage strains. Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD. © The Author 217. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Meningococcal Disease: Signs and Symptoms

MedlinePlus

... very serious and can be deadly in a matter of hours. Meningococcal Meningitis Doctors call meningitis caused ... Rapid breathing Diarrhea In the later stages, a dark purple rash ( see photos ) If you think you ...

Prevalence, Risk Factors and Molecular Characteristics of Meningococcal Carriage Among Brazilian Adolescents.

PubMed

Cassio de Moraes, Jose; Kemp, Brigina; de Lemos, Ana Paula Silva; Outeiro Gorla, Maria Cecilia; Lemes Marques, Eneida Gonçalves; Ferreira, Maria do Carmo; Sacchi, Claudio; Carvalhanas, Telma Regina Marques Pinto; Ribeiro, Ana Freitas; Ferreira, Cleide Marques; Salgado, Maristela Marques; Fukasawa, Lucila; Gonçalves, Maria Gisele; Higa, Fabio; Angerami, Rodrigo; Freitas, André Ribas; Sato, Helena Keico; Sáfadi, Marco Aurélio Palazzi

2015-11-01

In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children <2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students. A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11-19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed. The overall carriage prevalence was 9.9% (95% confidence interval, 8.3-11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains. The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil.

Prognostic markers of pediatric meningococcal sepsis.

PubMed

Briassoulis, George; Galani, Angeliki

2014-09-01

Having available tools to determine the prognosis of pediatric meningococcal sepsis at admission to the Intensive Care Unit or during the course of the disease constitutes a clinical necessity. Recently, new readily measurable circulating biomarkers have been described as an additional tool for severity classification and prediction of mortality in meningococcal disease. These biomarkers have been associated with increased risk of mortality scores and a number of organ failures in heterogeneous samples of critically ill children. In future, genetic markers may be used for identification of high-risk patients by creating prediction rules for clinical course and sequelae, and potentially provide more insight in the complex immune response in meningococcal sepsis. We briefly summarize the data pointing at the emerging genome-wide expression profiling studies and review the prognostic value of the main markers investigated in pediatric meningococcal sepsis putting them in the current frame of sepsis in general.

House-to-house, community-wide chemoprophylaxis for meningococcal disease: an aggressive approach to disease prevention.

PubMed Central

Chester, T J; Jacobson, J A; Caviness, E L; Wolf, F S

1977-01-01

During an outbreak of meningococcal disease in a rural community in southwest Alabama in 1975-76, we undertook an aggressive campaign of house-to-house, community-wide chemoprophylaxis distribution. Over a three-day period 1,045 households were visited and 4,454 persons received medication. The 1970 census lists 967 households with 4,067 persons residing in the community. To evaluate compliance we cultured for meningococcal carriers before and after the chemoprophylaxis campaign. All of the previously discovered carriers were negative three weeks after the drug distribution. The cost of the campaign ($26,520) was very small compared to the possible benefit achieved. The methods of planning and executing this campaign are described in detail. PMID:410314

Current safety issues with quadrivalent meningococcal conjugate vaccines.

PubMed

Myers, Tanya R; McNeil, Michael M

2018-05-04

Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra® (Sanofi Pasteur) and Menveo® (GlaxoSmithKline), and usage in the adolescent population has steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barré syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell's palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

Relevance of genetically determined host factors to the prognosis of meningococcal disease.

PubMed

Domingo, P; Muñiz-Diaz, E; Baraldès, M A; Arilla, M; Barquet, N; Pericas, R; Juárez, C; Madoz, P; Vázquez, G

2004-08-01

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, P<0.0001), and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval, 1.1-11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

On the trail of preventing meningococcal disease: a survey of students planning to travel to the United States.

PubMed

Huang, Hsien-Liang; Cheng, Shao-Yi; Lee, Long-Teng; Yao, Chien-An; Chu, Chia-Wei; Lu, Chia-Wen; Chiu, Tai-Yuan; Huang, Kuo-Chin

2013-01-01

College freshmen living in dormitories are at increased risk for meningococcal disease. Many students become a high-risk population when they travel to the United States. This study surveyed the knowledge, attitudes toward, and behavior surrounding the disease among Taiwanese college students planning to study in the United States, and to identify factors that may affect willingness to accept meningococcal vaccination. A cross-sectional survey of college students going to study in the United States was conducted in a medical center-based travel medicine clinic. Background information, attitudes, general knowledge, preventive or postexposure management, and individual preventive practices were collected through a structured questionnaire. A total of 358 students were included in the final analysis. More than 90% of participants believed that preventing meningococcal disease was important. However, fewer than 50% of students accurately answered six of nine questions exploring knowledge of the disease, and only 17.3% of students knew the correct management strategy after close contact with patients. Logistic regression analysis showed that students who understood the mode of transmission (odds ratio: 3.21, 95% CI = 1.117-9.229), medication management (1.88, 1.045-3.38), and epidemiology (2.735, 1.478-5.061) tended to be vaccinated. Despite an overall positive attitude toward meningococcal vaccination, there was poor knowledge about meningococcal disease. Promoting education on the mode of transmission, epidemiology, and pharmacological management of the disease could increase vaccination rates. Both the governments and travel medicine specialists should work together on developing an education program for this high-risk group other than just requiring vaccination. © 2013 International Society of Travel Medicine.

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

PubMed

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

2009-01-01

Meningococcal disease remains a serious public health problem worldwide. In Catalonia, after implementing the vaccination program, there has been a significant decrease in cases caused by meningococcus C. Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine in Catalonia. In < 6 years, the incidence rate of serogroup C fell from 7.6 to 0.6 per 100,000 persons/year in the periods before (1997-2000) and after (2001-2007) the introduction of the conjugate vaccine. In serogroup B, the reduction was from 15.4 to 11.1. In < 20 years case-fatality-rate increased only in serogroup B (3% and 7.4%). Serosubtype P1.15was the most frequent in serogroup B (31%), mainly associated with serotype 4 (80%), and in serogroup C subtype P1.5 (36%), with serotype 2a (86%). During 2008, 5 apparently unrelated cases of B:2a:P1.5 were identified in the same geographic area, with a case-fatality-rate of 80%. Exhaustive surveillance of circulating meningococcal strains is essential.

Carriage Rate and Effects of Vaccination after Outbreaks of Serogroup C Meningococcal Disease, Brazil, 2010

PubMed Central

Carvalhanas, Telma Regina Marques Pinto; Paula de Lemos, Ana; Gorla, Maria Cecilia Outeiro; Salgado, Maristela; Fukasawa, Lucila O.; Gonçalves, Maria Gisele; Higa, Fabio; Brandileone, Maria Cristina Cunto; Sacchi, Claudio Tavares; Ribeiro, Ana Freitas; Sato, Helena Keico; Bricks, Lucia Ferro; Cassio de Moraes, José

2014-01-01

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies. PMID:24751156

Invasive meningococcal disease in children in Jerusalem

PubMed Central

STEIN-ZAMIR, C.; ABRAMSON, N.; ZENTNER, G.; SHOOB, H.; VALINSKY, L.; BLOCK, C.

2008-01-01

SUMMARY Neisseria meningitidis is an important cause of childhood meningitis and septicaemia. Between 1999 and 2005, 133 invasive meningococcal disease (IMD) cases occurred in Jerusalem, 112 (84·2%) of them in children aged 0–14 years. The annual incidence rate in Jerusalem was higher than the national average (2·45±0·6 vs. 1·13±0·16/100 000 population, P=0·002). Most of the children (82·1%) were from low socio-economic Arab and Jewish ultra-orthodox communities; mortality was higher among Arab than Jewish children (1·3 vs. 0·22/100 000 person-years, P=0·004). A cluster of 10 children with severe meningococcal sepsis (three fatalities) emerged in the winter of 2003–2004. Compared to the other 102 cases in 1999–2005 both meningococcaemia (100% vs. 51%, P=0·003) and mortality (30% vs. 6·9%, P=0·014) rates were higher. Serogroup B comprised 77·6% of the bacterial isolates. Pulsed-field gel electrophoresis showed considerable variability among cluster isolates, but significant resemblance in Arab cases throughout 1999–2005. The increased susceptibility of specific sub-populations to IMD necessitates further evaluation. PMID:17662169

A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children.

PubMed

Knuf, M; Kieninger-Baum, D; Habermehl, P; Muttonen, P; Maurer, H; Vink, P; Poolman, J; Boutriau, D

2010-01-08

Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12-14 months) and 268 children (3-5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1 year of age.

Meningococcal ACWY Vaccines (MenACWY and MPSV4)

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts.Meningococcal ACWY vaccines can help prevent meningococcal disease caused by serogroups ...

Estimating costs associated with a community outbreak of meningococcal disease in a colombian Caribbean city.

PubMed

Pinzón-Redondo, Hernando; Coronell-Rodriguez, Wilfrido; Díaz-Martinez, Inés; Guzmán-Corena, Angel; Constenla, Dagna; Alvis-Guzmán, Nelson

2014-09-01

Meningococcal disease is a serious and potentially life-threatening infection that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is fatal in 9-12% of cases and with a death rate of up to 40% among patients with meningococcaemia. The objective of this study was to estimate the costs of a meningococcal outbreak that occurred in a Caribbean city of Colombia. We contacted experts involved in the outbreak and asked them specific questions about the diagnosis and treatment for meningococcal cases during the outbreak. Estimates of costs of the outbreak were also based on extensive review of medical records available during the outbreak. The costs associated with the outbreak were divided into the cost of the disease response phase and the cost of the disease surveillance phase. The costs associated with the outbreak control and surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the cases were reported to have meningitis (3/6); 33% were diagnosed with meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6); 66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine was not available at the time. The costs associated with control of the outbreak were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1 per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The costs associated with meningococcal outbreaks are substantial, and the outbreaks should be prevented. The mass chemoprophylaxis implemented helped control the outbreak.

Two Cases of Meningococcal Disease in One Family Separated by an Extended Period - Colorado, 2015-2016.

PubMed

Spence Davizon, Emily; Soeters, Heidi M; Miller, Lisa; Barnes, Meghan

2018-03-30

On April 26, 2015, a case of meningococcal disease in a woman aged 75 years was reported to the Colorado Department of Public Health and Environment (CDPHE). As part of routine public health investigation and control activities, all seven family contacts of the patient were advised to receive appropriate postexposure prophylaxis (PEP) to eradicate nasopharyngeal carriage of meningococci and prevent secondary disease (1), although it is not known whether the family contacts complied with PEP recommendations. Fifteen months later, on June 6, 2016, CDPHE was notified that the grandchild of the first patient, a male infant aged 3 months who lived with the first patient, also had meningococcal disease. The infant's immediate family members (parents and one sibling) were among family contacts for whom PEP was recommended in 2015. Neisseria meningitidis isolates from both patients were found to be serogroup C at the CDPHE laboratory. Whole genome sequence (WGS) analysis at CDC found that both isolates had the same sequence type, indicating close genetic relatedness. These cases represent a possible instance of meningococcal disease transmission within a family, despite appropriate PEP recommendations and with a long interval between cases.

Managing Meningococcal Disease (Septicaemia or Meningitis) in Higher Education Institutions. Guidelines

ERIC Educational Resources Information Center

Universities UK, 2004

2004-01-01

Students face many pressures today--pressure to be successful, financial worries and uncertainty about future career prospects. Good health is often taken for granted. It has taken publicity about recurring cases on meningococcal disease at university to bring home to students, universities and their associated doctors that students are at risk.…

Changes in the evolution of meningococcal disease, 2001-2008, Catalonia (Spain).

PubMed

Martínez, Ana I; Dominguez, Angela; Oviedo, Manuel; Minguell, Sofia; Jansa, Josep M; Codina, Gemma; Vazquez, Julio A

2009-05-26

Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine. In <6 years, the incidence rate of serogroup C fell from 7.6 to 0.6 per 100,000 persons/year in the periods before (1997-2000) and after (2001-2007) the introduction of the conjugate vaccine. In serogroup B, the reduction was from 15.4 to 11.1. In <20 years case-fatality-rate increased only in serogroup B (3% and 7.4%, p=0.026). Serosubtype P1.15 was the most frequent in serogroup B (31%), mainly associated with serotype 4 (80%), and in serogroup C subtype P1.5 (36%), with serosubtype 2a (86%). Exhaustive surveillance of circulating meningococcal strains is essential.

[Prevention of serogroup B meningococcal disease using a four-component vaccine].

PubMed

Gil, A; Barranco, D; Batalla, J; Bayas, J M; Campins, M; Gorrotxategi Gorrotxategi, P; Lluch, J; Martinón-Torres, F; Mellado, M J; Moreno-Pérez, D; Uriel, B; Vázquez, J A

2014-04-01

Meningococcal disease is an infection caused by Neisseria meningitidis, and those of serogroup B are currently the most predominant. It has been difficult to create effective vaccines for this serogroup in order to modify or reduce its morbidity. The aim of this study was to review existing data on the new vaccine 4CMenB and its potential contribution to the prevention of this infection. A panel of 12 experts (from Pediatrics, Public Health and Vaccinology) conducted a literature search and prioritized 74 publications. A review of the vaccine was then prepared, which was discussed in a meeting and subsequently validated by e-mail. 4CMenB vaccine, based on four components (NadA, fHbp, NHBA and OMVnz), was designed by reverse vaccinology. The Meningococcal Antigen Typing System (MATS) shows a potential of 70-80% coverage of the strains in Europe. Clinical trials show that the vaccine is safe and immunogenic in infants, children, adolescents, and adults, and induces an anamnestic response. The incidence of fever is similar to systemic vaccines administered alone, but higher when co-administered with them, although the fever pattern is predictable and self-limited. It is compatible with the Spanish routine vaccines, and can be administered simultaneously with the currently available hexavalent and pentavalent vaccines, as well as the pneumococcal conjugate vaccine. The 4CMenB vaccine is the only strategy currently available to prevent meningococcal disease caused by serogroup B. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2013.

PubMed

MacNeil, Jessica R; Rubin, Lorry; McNamara, Lucy; Briere, Elizabeth C; Clark, Thomas A; Cohn, Amanda C

2014-06-20

During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased risk. This report summarizes information on MenACWY-CRM administration in infants and provides recommendations for vaccine use in infants aged 2 through 23 months who are at increased risk for meningococcal disease. Because the burden of meningococcal disease in infants is low in the United States and the majority of cases that do occur are caused by serogroup B, which is not included in any vaccine licensed in the United States, only those infants who are at increased risk for meningococcal disease are recommended to receive a meningococcal vaccine.

The prevalence, serogroup distribution and risk factors of meningococcal carriage in adolescents and young adults in Turkey

PubMed Central

Tekin, Rahmi Tuna; Dinleyici, Ener Cagri; Ceyhan, Mehmet; Karbuz, Adem; Salman, Nuran; Sutçu, Murat; Kurugol, Zafer; Balliel, Yasemin; Celik, Melda; Hacimustafaoglu, Mustafa; Kuyucu, Necdet; Kondolot, Meda; Sensoy, Gülnar; Metin, Ozge; Kara, Soner Sertan; Dinleyici, Meltem; Kılıç, Omer; Bayhan, Cihangul; Gurbuz, Venhar; Aycan, Emre; Memedova, Aygun; Karli, Arzu; Bozlu, Gulçin; Celebi, Solmaz

2017-01-01

ABSTRACT The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10–24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10–14 age group, 6.4% in the 15–17 age-group, and 4.7% in the 18–20 age group; the highest carriage rate was found in the 21–24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants

The prevalence, serogroup distribution and risk factors of meningococcal carriage in adolescents and young adults in Turkey.

PubMed

Tekin, Rahmi Tuna; Dinleyici, Ener Cagri; Ceyhan, Mehmet; Karbuz, Adem; Salman, Nuran; Sutçu, Murat; Kurugol, Zafer; Balliel, Yasemin; Celik, Melda; Hacimustafaoglu, Mustafa; Kuyucu, Necdet; Kondolot, Meda; Sensoy, Gülnar; Metin, Ozge; Kara, Soner Sertan; Dinleyici, Meltem; Kılıç, Omer; Bayhan, Cihangul; Gurbuz, Venhar; Aycan, Emre; Memedova, Aygun; Karli, Arzu; Bozlu, Gulçin; Celebi, Solmaz

2017-05-04

The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10-24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10-14 age group, 6.4% in the 15-17 age-group, and 4.7% in the 18-20 age group; the highest carriage rate was found in the 21-24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close

An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children.

PubMed

Knuf, Markus; Pantazi-Chatzikonstantinou, Anna; Pfletschinger, Ulrich; Tichmann-Schumann, Irmingard; Maurer, Hartwig; Maurer, Lothar; Fischbach, Thomas; Zinke, Henrike; Pankow-Culot, Heidemarie; Papaevangelou, Vassiliki; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2011-06-06

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prolonged university outbreak of meningococcal disease associated with a serogroup B strain rarely seen in the United States.

PubMed

Mandal, Sema; Wu, Henry M; MacNeil, Jessica R; Machesky, Kimberly; Garcia, Jocelyn; Plikaytis, Brian D; Quinn, Kim; King, Larry; Schmink, Susanna E; Wang, Xin; Mayer, Leonard W; Clark, Thomas A; Gaskell, James R; Messonnier, Nancy E; DiOrio, Mary; Cohn, Amanda C

2013-08-01

College students living in residential halls are at increased risk of meningococcal disease. Unlike that for serogroups prevented by quadrivalent meningococcal vaccines, public health response to outbreaks of serogroup B meningococcal disease is limited by lack of a US licensed vaccine. In March 2010, we investigated a prolonged outbreak of serogroup B disease associated with a university. In addition to case ascertainment, molecular typing of isolates was performed to characterize the outbreak. We conducted a matched case-control study to examine risk factors for serogroup B disease. Five controls per case, matched by college year, were randomly selected. Participants completed a risk factor questionnaire. Data were analyzed using conditional logistic regression. Between January 2008 and November 2010, we identified 13 meningococcal disease cases (7 confirmed, 4 probable, and 2 suspected) involving 10 university students and 3 university-linked persons. One student died. Ten cases were determined to be serogroup B. Isolates from 6 confirmed cases had an indistinguishable pulsed-field gel electrophoresis pattern and belonged to sequence type 269, clonal complex 269. Factors significantly associated with disease were Greek society membership (matched odds ratio [mOR], 15.0; P = .03), >1 kissing partner (mOR, 13.66; P = .03), and attending bars (mOR, 8.06; P = .04). The outbreak was associated with a novel serogroup B strain (CC269) and risk factors were indicative of increased social mixing. Control measures were appropriate but limited by lack of vaccine. Understanding serogroup B transmission in college and other settings will help inform use of serogroup B vaccines currently under consideration for licensure.

Estimating Costs Associated with a Community Outbreak of Meningococcal Disease in a Colombian Caribbean City

PubMed Central

Pinzón-Redondo, Hernando; Coronell-Rodriguez, Wilfrido; Díaz-Martinez, Inés; Guzmán-Corena, Ángel; Constenla, Dagna

2014-01-01

ABSTRACT Meningococcal disease is a serious and potentially life-threatening infection that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is fatal in 9-12% of cases and with a death rate of up to 40% among patients with meningococcaemia. The objective of this study was to estimate the costs of a meningococcal outbreak that occurred in a Caribbean city of Colombia. We contacted experts involved in the outbreak and asked them specific questions about the diagnosis and treatment for meningococcal cases during the outbreak. Estimates of costs of the outbreak were also based on extensive review of medical records available during the outbreak. The costs associated with the outbreak were divided into the cost of the disease response phase and the cost of the disease surveillance phase. The costs associated with the outbreak control and surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the cases were reported to have meningitis (3/6); 33% were diagnosed with meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6); 66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine was not available at the time. The costs associated with control of the outbreak were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1 per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The costs associated with meningococcal outbreaks are substantial, and the outbreaks should be prevented. The mass chemoprophylaxis implemented helped control the outbreak. PMID:25395916

Baseline Meningococcal Carriage in Burkina Faso before the Introduction of a Meningococcal Serogroup A Conjugate Vaccine▿

PubMed Central

Kristiansen, Paul A.; Diomandé, Fabien; Wei, Stanley C.; Ouédraogo, Rasmata; Sangaré, Lassana; Sanou, Idrissa; Kandolo, Denis; Kaboré, Pascal; Clark, Thomas A.; Ouédraogo, Abdoul-Salam; Absatou, Ki Ba; Ouédraogo, Charles D.; Hassan-King, Musa; Thomas, Jennifer Dolan; Hatcher, Cynthia; Djingarey, Mamoudou; Messonnier, Nancy; Préziosi, Marie-Pierre; LaForce, Marc; Caugant, Dominique A.

2011-01-01

The serogroup A meningococcal conjugate vaccine MenAfriVac has the potential to confer herd immunity by reducing carriage prevalence of epidemic strains. To better understand this phenomenon, we initiated a meningococcal carriage study to determine the baseline carriage rate and serogroup distribution before vaccine introduction in the 1- to 29-year old population in Burkina Faso, the group chosen for the first introduction of the vaccine. A multiple cross-sectional carriage study was conducted in one urban and two rural districts in Burkina Faso in 2009. Every 3 months, oropharyngeal samples were collected from >5,000 randomly selected individuals within a 4-week period. Isolation and identification of the meningococci from 20,326 samples were performed by national laboratories in Burkina Faso. Confirmation and further strain characterization, including genogrouping, multilocus sequence typing, and porA-fetA sequencing, were performed in Norway. The overall carriage prevalence for meningococci was 3.98%; the highest prevalence was among the 15- to 19-year-olds for males and among the 10- to 14-year-olds for females. Serogroup Y dominated (2.28%), followed by serogroups X (0.44%), A (0.39%), and W135 (0.34%). Carriage prevalence was the highest in the rural districts and in the dry season, but serogroup distribution also varied by district. A total of 29 sequence types (STs) and 51 porA-fetA combinations were identified. The dominant clone was serogroup Y, ST-4375, P1.5-1,2-2/F5-8, belonging to the ST-23 complex (47%). All serogroup A isolates were ST-2859 of the ST-5 complex with P1.20,9/F3-1. This study forms a solid basis for evaluating the impact of MenAfriVac introduction on serogroup A carriage. PMID:21228139

Challenges and opportunities for meningococcal vaccination in the developing world.

PubMed

Shaker, Rouba; Fayad, Danielle; Dbaibo, Ghassan

2018-05-04

Meningococcal disease continues to be a life threatening infection with high morbidity and mortality even in appropriately treated patients. Meningococcal vaccination plays a major role in the control of the disease; however, implementing vaccination remains problematic in the developing world. The objective of this review is to identify the challenges facing the use of meningococcal vaccines in the developing world in order to discuss the opportunities and available solutions to improve immunization in these countries. Inadequate epidemiologic information necessary to implement vaccination and financial challenges predominate. Multiple measures are needed to achieve the successful implementation of meningococcal conjugate vaccination programs that protect against circulating serogroups in developing countries including enhanced surveillance systems, financial support and aid through grants, product development partnerships that are the end result of effective collaboration and communication between different interdependent stakeholders to develop affordable vaccines, and demonstration of the cost-effectiveness of new meningococcal vaccines.

Introducing vaccination against serogroup B meningococcal disease: An economic and mathematical modelling study of potential impact

PubMed Central

Christensen, Hannah; Hickman, Matthew; Edmunds, W. John; Trotter, Caroline L.

2013-01-01

Background Meningococcal disease remains an important cause of morbidity and mortality worldwide. The first broadly effective vaccine against group B disease (which causes considerable meningococcal disease in Europe, the Americas and Australasia) was licensed in the EU in January 2013; our objective was to estimate the potential impact of introducing such a vaccine in England. Methods We developed two models to estimate the impact of introducing a new ‘MenB’ vaccine. The cohort model assumes the vaccine protects against disease only; the transmission dynamic model also allows the vaccine to protect against carriage (accounting for herd effects). We used these, and economic models, to estimate the case reduction and cost-effectiveness of a number of different vaccine strategies. Results We estimate 27% of meningococcal disease cases could be prevented over the lifetime of an English birth cohort by vaccinating infants at 2,3,4 and 12 months of age with a vaccine that prevents disease only; this strategy could be cost-effective at £9 per vaccine dose. Substantial reductions in disease (71%) can be produced after 10 years by routinely vaccinating infants in combination with a large-scale catch-up campaign, using a vaccine which protects against carriage as well as disease; this could be cost-effective at £17 per vaccine dose. Conclusions New ‘MenB’ vaccines could substantially reduce disease in England and be cost-effective if competitively priced, particularly if the vaccines can prevent carriage as well as disease. These results are relevant to other countries, with a similar epidemiology to England, considering the introduction of a new ‘MenB’ vaccine. PMID:23566946

Does Dexamethasone Helps in Meningococcal Sepsis?

PubMed

Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-06-01

Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.

Meningococcal serogroup Y emergence in Europe

PubMed Central

Bröker, Michael; Bukovski, Suzana; Culic, Davor; Jacobsson, Susanne; Koliou, Maria; Kuusi, Markku; Simões, Maria João; Skoczynska, Anna; Toropainen, Maija; Taha, Muhamed-Keir; Tzanakaki, Georgina

2014-01-01

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal.1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low. PMID:24608912

Does Dexamethasone Helps in Meningococcal Sepsis?

PubMed Central

Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-01-01

Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease. PMID:28974828

Serogroup B Meningococcal vaccine (MenB) - What you need to know

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts. Serogroup B meningococcal (MenB) vaccines can help prevent meningococcal disease caused by serogroup ...

Use of MenACWY-CRM in adolescents in the United States.

PubMed

Black, Steven; Block, Stan L

2013-03-01

Adolescents constitute a high-risk group for invasive meningococcal disease. MenACWY-CRM (Menveo, Novartis Vaccines, Cambridge, MA) is a quadrivalent meningococcal conjugate vaccine indicated to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W-135, and Y. It has been approved for use in persons age 2-55 years. The tolerability and immunogenicity of MenACWY-CRM in adolescents have been ascertained in phase 2 and 3 trials against MPSV4 (Menomune, sanofi pasteur, Swiftwater, PA), an unconjugated quadrivalent meningococcal vaccine, and MenACWY-D (Menactra, sanofi pasteur), another conjugated quadrivalent meningococcal vaccine. Clinical trials also have demonstrated that MenACWY-CRM is well tolerated and immunogenic when administered to adolescents concomitantly with the combined tetanus, diphtheria, and acellular pertussis vaccine (Boostrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent human papillomavirus vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Immune memory in children previously vaccinated with an experimental quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine.

PubMed

Pichichero, Michael; Papa, Thomas; Blatter, Mark; Mitchell, Douglas; Kratz, Richard; Sneed, Jane; Bassily, Ehab; Casey, Janet; Gilmet, Gregory

2006-11-01

In a previous study, a meningococcal diphtheria toxoid conjugate vaccine (MCV-4) triggered robust bactericidal antibody responses against serogroups A, C, Y, and W-135 in 2- to 10-year-old children. A subset of participants, 2 to 3 years of age at the initial vaccination, was evaluated for persistence of antibody, immune memory, and antibody avidity. Participants were healthy children vaccinated 23 to 36 months earlier with MCV-4 (primed) or newly recruited meningococcal vaccine-naive 4-year-olds. Participants in both groups were alternately allocated to provide sera 8 or 28 days after administration of one tenth of the recommended dose of a meningococcal polysaccharide vaccine (PSV-4). Immune responses were assessed in sera obtained at baseline and either 8 or 28 days after reduced-dose PSV-4 administration. Safety was monitored. Before PSV-4 challenge, serum bactericidal antibody geometric mean titers (SBA GMTs) were higher for all 4 serogroups in the MCV-4-primed group than in the vaccine-naive group. SBA GMTs, geometric mean concentrations of immunoglobulin G (IgG) and geometric mean avidity indices for all 4 serogroups were significantly higher among MCV-4-primed versus vaccine-naive participants in the cohorts evaluated at 8 or 28 days after PSV-4 challenge. Adverse events were generally mild, self-limited, and comparable in all groups of children. Persistence of bactericidal antibody was seen for 23 to 36 months after a primary dose of MCV-4 in young children. Booster responses and avidity maturation were evident after a challenge with reduced-dose polysaccharide vaccine.

Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®).

PubMed

Gandhi, Ashesh; Balmer, Paul; York, Laura J

2016-08-01

Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.

[Polyvalent meningococcal vaccines: within or outside our agenda?].

PubMed

Abad, R; Vázquez, J A

2014-11-01

The development of tetravalent vaccines against Invasive Meningococcal Disease (IMD) has been driven mainly due to the increase of the prevalence and geographic expansion of several serogroups considered unusual, but also because of the need for vaccines that offer broad spectrum protection in a devastating disease such as IMD. These changes in serogroups considered usual (B and C) have been detected for both serogroup Y and W, which has led to the multivalent vaccines being used by a number of countries with different strategies that will be discussed in the article. Epidemiological data in Spain, currently do not justify its use in immunization schedules, but there is a potential risk for the introduction of virulent clones of those uncommon serogroups (Y and W), and this would lead us to open a discussion of their potential use, particularly in the adolescent/pre-teen population as a target group for intervention. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Meningococcal meningitis C in Tamil Nadu, public health perspectives.

PubMed

David, Kirubah Vasandhi; Pricilla, Ruby Angeline; Thomas, Beeson

2014-01-01

Meningococcal meningitis has rarely been reported in Tamil Nadu. We report here two children diagnosed with meningococcal meningitis in Vellore, Tamil Nadu, on May 2014. The causative strain was Neisseria meningitidis serotype C. The role of the primary care physician in early diagnosis, appropriate referral, and preventive measures of this disease to the immediate family and community is stressed.

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.

PubMed

Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

2010-11-01

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.

Meningococcal ACWY Vaccines - MenACWY and MPSV4: What You Need to Know

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts. Meningococcal ACWY vaccines can help prevent meningococcal disease caused by serogroups ...

Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

PubMed

Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

2016-07-03

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

PubMed Central

van Deuren, Marcel; Brandtzaeg, Petter; van der Meer, Jos W. M.

2000-01-01

The only natural reservoir of Neisseria meningitidis is the human nasopharyngeal mucosa. Depending on age, climate, country, socioeconomic status, and other factors, approximately 10% of the human population harbors meningococci in the nose. However, invasive disease is relatively rare, as it occurs only when the following conditions are fulfilled: (i) contact with a virulent strain, (ii) colonization by that strain, (iii) penetration of the bacterium through the mucosa, and (iv) survival and eventually outgrowth of the meningococcus in the bloodstream. When the meningococcus has reached the bloodstream and specific antibodies are absent, as is the case for young children or after introduction of a new strain in a population, the ultimate outgrowth depends on the efficacy of the innate immune response. Massive outgrowth leads within 12 h to fulminant meningococcal sepsis (FMS), characterized by high intravascular concentrations of endotoxin that set free high concentrations of proinflammatory mediators. These mediators belonging to the complement system, the contact system, the fibrinolytic system, and the cytokine system induce shock and diffuse intravascular coagulation. FMS can be fatal within 24 h, often before signs of meningitis have developed. In spite of the increasing possibilities for treatment in intensive care units, the mortality rate of FMS is still 30%. When the outgrowth of meningococci in the bloodstream is impeded, seeding of bacteria in the subarachnoidal compartment may lead to overt meningitis within 24 to 36 h. With appropriate antibiotics and good clinical surveillance, the mortality rate of this form of invasive disease is 1 to 2%. The overall mortality rate of meningococcal disease can only be reduced when patients without meningitis, i.e., those who may develop FMS, are recognized early. This means that the fundamental nature of the disease as a meningococcus septicemia deserves more attention. PMID:10627495

Cluster of Serogroup W135 Meningococci, Southeastern Florida, 2008–2009

PubMed Central

Mejia-Echeverry, Alvaro; Fiorella, Paul; Leguen, Fermin; Livengood, John; Kay, Robyn; Hopkins, Richard

2010-01-01

Recently, 14 persons in southeastern Florida were identified with Neisseria meningitidis serogroup W135 invasive infections. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to the multilocus sequence type 11 clonal complex. The epidemiologic investigation suggested recent endemic transmission of this clonal complex in southeastern Florida. PMID:20031054

Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands.

PubMed

Bousema, Josefien Cornelie Minthe; Ruitenberg, Joost

2015-09-13

Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries. © 2015 by Kerman University of Medical Sciences.

Naturally Occurring Lipid A Mutants in Neisseria meningitidis from Patients with Invasive Meningococcal Disease Are Associated with Reduced Coagulopathy

PubMed Central

Fransen, Floris; Heckenberg, Sebastiaan G. B.; Hamstra, Hendrik Jan; Feller, Moniek; Boog, Claire J. P.; van Putten, Jos P. M.; van de Beek, Diederik

2009-01-01

Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system

Predictors of Meningococcal Vaccination among University Students

ERIC Educational Resources Information Center

D'Heilly, Sarah; Ehlinger, Edward; Nichol, Kristin

2006-01-01

Invasive disease secondary to Neisseria meningitidis is a rare but devastating illness among university students. The Advisory Committee on Immunization Practices recommends educating college freshmen about meningococcal disease and vaccinating all college freshmen who live in residence halls. We conducted this survey to gain a better…

Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock.

PubMed

Bjerre, Anna; Brusletto, Berit; Høiby, Ernst Arne; Kierulf, Peter; Brandtzaeg, Petter

2004-02-01

To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. Experimental study. Laboratory. Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. We speculate whether high concentrations of interleukin-10 contribute to the

Safety and immunogenicity of a booster dose of meningococcal (groups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine.

PubMed

Robertson, Corwin A; Greenberg, David P; Hedrick, James; Pichichero, Michael; Decker, Michael D; Saunders, Martha

2016-10-17

Quadrivalent meningococcal conjugate vaccines (MenACWY) were developed to offer long-term protection against invasive disease caused by serogroups A, C, W, and Y. Reduced MenACWY effectiveness within 5 years after primary vaccination (likely due to declining bactericidal antibody titers) has been described, particularly with respect to C and Y disease in the United States. We evaluated the safety and immunogenicity of a single booster dose of quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) in adolescents and adults who received a previous dose 4-6 years earlier. This phase 2, open-label, multicenter study of 834 persons was conducted in the United States. Participants received a single 0.5-mL booster dose of MenACWY-D. Serogroup-specific bactericidal antibody geometric mean titers (GMTs) were measured with a serum bactericidal antibody assay using human complement (hSBA). Proportions of participants achieving antibody titers of ⩾1:8 for each vaccine serogroup on Days 6 and 28 were determined. Rates of adverse events (AEs), including serious adverse events (SAEs), were also assessed. Before booster vaccination, 38.7-68.5% of participants had an hSBA titer ⩾1:8, depending on vaccine serogroup. By Day 6 post-vaccination, 98.2-99.1% of participants had hSBA titers ⩾1:8. By Day 28, >99% of participants achieved this threshold and the primary hypothesis (lower limit of the one-sided 95% confidence limit ⩾85% for each serogroup) was met. The GMT ratios (post-vaccination divided by pre-vaccination) at Day 28 ranged from 47.2 (serogroup A) to 209.1 (serogroup Y). Rates of AEs, including SAEs, were similar to those observed among adolescents and adults who received a primary dose of MenACWY-D in previous studies. There were no study discontinuations due to an AE and no deaths. Booster vaccination with MenACWY-D was safe and induced robust bactericidal antibody responses, consistent with immune memory, among adolescents and

Update on invasive meningococcal vaccination for Canadian children and youth.

PubMed

Robinson, Joan L

2018-02-01

Invasive meningococcal disease (IMD) is serious, often resulting in fulminant sepsis or meningitis. IMD in Canada is primarily attributable to serogroups B and C. There are routine programs for serogroup C vaccine at 12 months of age, with some jurisdictions routinely providing additional earlier doses. Adolescents routinely receive a booster dose of serogroup C vaccine or of a quadrivalent (serogroups A, C, W and Y) vaccine. Serogroup B vaccines are not recommended for routine use pending further data on the efficacy and duration of protection from the available vaccine. However, children at increased risk for IMD should start immunization for serogroups B and C as soon as possible, assuming that they are at least 2 months of age.

Association of a Bacteriophage with Meningococcal Disease in Young Adults

PubMed Central

Gray, Stephen J.; Kaczmarski, Edward B.; McCarthy, Noel D.; Nassif, Xavier; Maiden, Martin C. J.; Tinsley, Colin R.

2008-01-01

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases. PMID:19065260

An outbreak of serogroup C (ST-11) meningococcal disease in Tijuana, Mexico.

PubMed

Chacon-Cruz, Enrique; Espinosa-De Los Monteros, Luz Elena; Navarro-Alvarez, Samuel; Aranda-Lozano, Jose Luis; Volker-Soberanes, Maria Luisa; Rivas-Landeros, Rosa Maria; Alvelais-Arzamendi, Ariadna Annete; Vazquez, Julio Alberto

2014-05-01

Invasive meningococcal disease (IMD) has been reported to be endemic in children from Tijuana, Mexico and the risk of an outbreak was always a threat. To describe all clinical, epidemiological and microbiological features of a meningococcal outbreak that occurred in Tijuana, Mexico. All cases with IMD were admitted at different emergency departments within the city and diagnosed by culture and agglutination tests. Further restriction fragment length polymorphism pulse field gel electrophoresis (RFLP-PFGE) and multi locus sequence typing (MLST) were performed. All clinical and epidemiological characteristics and interventions were evaluated, as well as risk factors associated with mortality. From 30 January 2013 to 30 March 2013 there were 19 cases of IMD all caused by Neisseria meningitidis serogroup C. The median age was 16 years (2-47), with higher frequency among individuals at least 13 years old (73.7%). At admission, meningitis was the main clinical presentation (94.7%), followed by purpura (78.9%), septic shock (42.1%) and disseminated intravascular coagulation (DIC, 36.8%). Overall mortality was seven (36.8%). Variables associated with higher mortality were, at admission, presence of septic shock, DIC and thrombocytopenia less than 70,000. All 19 cases had no identifiable site or cluster as the source of the outbreak. RFLP-PFGE showed a discriminatory power for only one profile on all N. meningitidis strains analyzed and a clone ST-11 was identified in all strains. Public health interventions were continuous case reporting of all suspected cases of IMD, an increase in active surveillance in all hospitals, training of medical and laboratory personnel, massive and rapid chemoprophylaxis to all close contacts as indicated, and promotion of good health habits. An outbreak with high mortality of IMD occurred in Tijuana, Mexico. This event and evidence of endemicity should encourage health authorities to evaluate meningococcal vaccination in the region.

Immunogenicity of a Booster Dose of Quadrivalent Meningococcal Conjugate Vaccine in Previously Immunized HIV-Infected Children and Youth.

PubMed

Warshaw, Meredith G; Siberry, George K; Williams, Paige; Decker, Michael D; Jean-Philippe, Patrick; Lujan-Zilbermann, Jorge

2017-09-01

The US Advisory Committee on Immunization Practices recommends a booster dose of quadrivalent meningococcal conjugate vaccine (MCV4) after initial immunization for patients at high risk for meningococcal infection. The International Maternal Pediatric Adolescents AIDS Clinical Trials (IMPAACT) P1065 trial evaluated the use of MCV4 in human immunodeficiency virus (HIV)-infected children and youth. The final step of this trial was an open-label study of an MCV4 booster dose 3.5 years after primary MCV4 immunization. Antibody titers were evaluated at the time of the booster vaccine and 1, 4, and 24 weeks after the booster. Immunogenicity was measured by rabbit serum bactericidal antibody (rSBA) against each meningococcal serogroup. Immunologic memory was defined as either seroprotection (rSBA titer ≥1:128) or a ≥4-fold increase 1 week after the booster dose. Primary response was defined as either a ≥4-fold response or seropositivity 4 weeks after the booster in the absence of immunologic memory. Adverse events were assessed for 4 weeks after the booster dose. Of 174 participants with serology results at entry and 1 and 4 weeks later, the percentage with protective antibody levels at entry varied according to serogroup, ranging from a low of 26% for serogroup C to a high of 68% for serogroup A. A memory response to at least 1 serogroup occurred in 98% of the participants: 93% each for serogroups A and Y, 88% for serogroup C, and 94% for serogroup W-135; 83% had a memory response to all 4 serogroups. Overall, rates of any memory or primary response were ≥90% for all serogroups. No serious adverse events were encountered. A booster dose of MCV4 elicited a memory response in 88% to 94% of previously immunized HIV-infected participants depending on serogroup, including those who lacked a protective titer level for that serogroup before booster vaccination. © The Author 2017. Published by the Oxford University Press on behalf of The Journal of the Pediatric

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

PubMed

Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Splenic cyst and its management in a 21-month-old boy: a rare complication of invasive meningococcal disease.

PubMed

Pratt, Jeremy John; Connell, Tom G; Bekhit, Elhamy; Crawford, Nigel W

2018-05-04

Splenic complications of invasive meningococcal disease (IMD) are well recognised, though cyst formation is rare, particularly in paediatric populations. The best approach to their management is not yet established. This case outlines the management of a splenic cyst in a 21-month-old boy following severe IMD. The case took place in the context of an acute emergence of serogroup W prompting significant media attention and subsequent change in vaccination practice at a jurisdictional level in Australia. The patient was critically unwell early in the illness, then later a collection in the left upper quadrant was detected, shown on ultrasound to be a 11.6×7.7 cm splenic cyst. In this case, the cyst was managed by ultrasound-guided drainage tube insertion. The residual collection was small and stable on subsequent imaging. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

PubMed

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

2017-02-01

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

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

PubMed

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Can near real-time monitoring of emergency department diagnoses facilitate early response to sporadic meningococcal infection? - prospective and retrospective evaluations

PubMed Central

2010-01-01

Background Meningococcal infection causes severe, rapidly progressing illness and reporting of cases is mandatory in New South Wales (NSW), Australia. The NSW Department of Health operates near real-time Emergency Department (ED) surveillance that includes capture and statistical analysis of clinical preliminary diagnoses. The system can provide alerts in response to specific diagnoses entered in the ED computer system. This study assessed whether once daily reporting of clinical diagnoses of meningococcal infection using the ED surveillance system provides an opportunity for timelier public health response for this disease. Methods The study involved a prospective and retrospective component. First, reporting of ED diagnoses of meningococcal infection from the ED surveillance system prospectively operated in parallel with conventional surveillance which requires direct telephone reporting of this scheduled medical condition to local public health authorities by hospitals and laboratories when a meningococcal infection diagnosis is made. Follow-up of the ED diagnoses determined whether meningococcal infection was confirmed, and the time difference between ED surveillance report and notification by conventional means. Second, cases of meningococcal infection reported by conventional surveillance during 2004 were retrospectively matched to ED visits to determine the sensitivity and positive predictive value (PPV) of ED surveillance. Results During the prospective evaluation, 31 patients were diagnosed with meningococcal infection in participating EDs. Of these, 12 had confirmed meningococcal disease, resulting in a PPV of 38.7%. All confirmed cases were notified earlier to public health authorities by conventional reporting. Of 149 cases of notified meningococcal disease identified retrospectively, 130 were linked to an ED visit. The sensitivity and PPV of the ED diagnosis for meningococcal infection was 36.2% and 36.7%, respectively. Conclusions Based on prospective

New Meningococcal Vaccine Recommendations under Consideration

ERIC Educational Resources Information Center

Turner, James C.

2004-01-01

The Advisory Committee on Immunization Practices (ACIP) at the Center for Disease Control and Prevention (CDC) will be considering a new vaccination recommendation for the prevention of invasive "N. meningitidis" infection when meningococcal conjugate vaccines are licensed in the United States. The CDC has also updated the Working Group…

Phase 1 first-in-human studies of the reactogenicity and immunogenicity of a recombinant meningococcal NspA vaccine in healthy adults.

PubMed

Halperin, Scott A; Langley, Joanne M; Smith, Bruce; Wunderli, Peter; Kaufman, Lisa; Kimura, Alan; Martin, Denis

2007-01-05

Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Healthy 18-50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune((R))). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125mug dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies.

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2016-01-01

Purpose 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., Methods 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). Results 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. Conclusion 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. PMID:27907129

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

PubMed

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

2016-01-01

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

Meningococcal vaccines: Current state and future outlook.

PubMed

Leca, M; Bornet, C; Montana, M; Curti, C; Vanelle, P

2015-06-01

Neisseria meningitidis infections are a major public health problem worldwide. Although conventional approaches have not led to development of a serogroup B meningococcal vaccine, a new technique based on genome sequencing has created new perspectives. Recently, a universal serogroup B meningococcal vaccine, Bexsero(®), was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety. Availability of this vaccine could contribute positively to human health, by significantly reducing the incidence of meningococcal infections. However, unfavorable cost-effectiveness analysis means that routine vaccination is not currently recommended. Another serogroup meningococcal vaccine, Trumemba(®), was also recently licensed in United States. Like any drug, Bexsero(®) and Trumemba(®) will require close observation to assess their impact on meningococcal epidemiology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile.

PubMed

Tappero, J W; Lagos, R; Ballesteros, A M; Plikaytis, B; Williams, D; Dykes, J; Gheesling, L L; Carlone, G M; Høiby, E A; Holst, J; Nøkleby, H; Rosenqvist, E; Sierra, G; Campa, C; Sotolongo, F; Vega, J; Garcia, J; Herrera, P; Poolman, J T; Perkins, B A

1999-04-28

Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group. To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy. Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994. Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993. Infants younger than 1 year (n = 187), children aged 2 to 4 years (n = 183), and adults aged 17 to 30 years (n = 173). Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3. Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer. Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen. These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic

Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines.

PubMed

Tontini, M; Berti, F; Romano, M R; Proietti, D; Zambonelli, C; Bottomley, M J; De Gregorio, E; Del Giudice, G; Rappuoli, R; Costantino, P; Brogioni, G; Balocchi, C; Biancucci, M; Malito, E

2013-10-01

Glycoconjugate vaccines are among the most effective and safest vaccines ever developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been mostly used as protein carriers in licensed vaccines. We evaluated the immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides conjugated to CRM197, DT and TT in naïve mice. The three carriers were equally efficient in inducing an immune response against the carbohydrate moiety in immunologically naïve mice. The effect of previous exposure to different dosages of the carrier protein on the anti-carbohydrate response was studied using serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed a strong propensity to positively prime the anti-carbohydrate response elicited by its conjugates or those with the antigenically related carrier DT. Conversely in any of the tested conditions TT priming did not result in enhancement of the anti-carbohydrate response elicited by the corresponding conjugates. Repeated exposure of mice to TT or to CRM197 before immunization with the respective MenA conjugates resulted in a drastic suppression of the anti-carbohydrate response in the case of TT conjugate and only in a slight reduction in the case of CRM197. The effect of carrier priming on the anti-MenA response of DT-based conjugates varied depending on their carbohydrate to protein ratio. These data may have implications for human vaccination since conjugate vaccines are widely used in individuals previously immunized with DT and TT carrier proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Epidemic meningitis in 2013 in Republic of Guinea: Nesseria meningitidis W135 emergence].

PubMed

Traoré, F A; Sako, F B; Sylla, D; Kader, D S; Bangoura, M; Traoré, M; Keita, A; Sidibé, A; Keita, S; Barry, M; Cisse, M; Touré, A

2016-12-01

A prospective study conducted from 1 January to 31 December 2013 described a meningitis epidemic in Republic of Guinea. The identification of the germs was based on Gram stain, latex agglutination and culture. During the study period, 480 suspected cases of meningitis were reported by 21 health districts. The average age was 18±8 years and 62.5% were men. The vaccination status was unknown in all patients. The largest attack rates were found in Siguiri (3.2 per 10,000), Kankan (2.6 per 10,000) and Dabola (3.9 per 10,000). The locality of Kintinian in Siguiri was the only one to cross the epidemic threshold. The identified microorganisms were Haemophilus influenzae (1 time), Pneumococcus (2 times), Neisseria meningitidis A (4 times) and W135 (10 times) with a total of 17 positive samples. All of these germs were sensitive to chloramphenicol, ceftriaxone and ciprofloxacin. The average hospital stay was 6.5±2 days. The lethality was 13.8%. This meningitis epidemic was characterized by the emergence of Neisseria meningitidis W135. The monitoring of this serogroup should be increased and future vaccination strategies must include it presence.

[Meningococcal vaccines. Global epidemiological situation and strategies for prevention by vaccination].

PubMed

Rivero Calle, Irene; Rodriguez-Tenreiro Sánchez, Carmen; Martinón-Torres, Federico

2015-04-01

N. meningitidis is a major cause of meningitis and septicemia and a major public health problem in many countries. The disease, that can be fulminant, has a high mortality and may cause serious sequelae, even in cases of apparently optimal medical treatment. Chemoprophylaxis may prevent secondary cases among those in close contact with the ill, but, since secondary cases represent only 1%-2% of all meningococcal disease, chemoprophylaxis has a small impact when fighting most of endemic and epidemic forms. Given that al least 5% -15% of children and young adults are carriers, the fight against meningococcal disease based on chemotherapeutic elimination of nasopharyngeal colonization is virtually impossible. Therefore, immunization is the only rational way to combat this disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Economics of an adolescent meningococcal conjugate vaccination catch-up campaign in the United States.

PubMed

Ortega-Sanchez, Ismael R; Meltzer, Martin I; Shepard, Colin; Zell, Elizabeth; Messonnier, Mark L; Bilukha, Oleg; Zhang, Xinzhi; Stephens, David S; Messonnier, Nancy E

2008-01-01

In June 2005, the Advisory Committee on Immunization Practices recommended the newly licensed quadrivalent meningococcal conjugate vaccine for routine use among all US children aged 11 years. A 1-time catch-up vaccination campaign for children and adolescents aged 11-17 years, followed by routine annual immunization of each child aged 11 years, could generate immediate herd immunity benefits. The objective of our study was to analyze the cost-effectiveness of a catch-up vaccination campaign with quadrivalent meningococcal conjugate vaccine for children and adolescents aged 11-17 years. We built a probabilistic model of disease burden and economic impacts for a 10-year period with and without a program of adolescent catch-up meningococcal vaccination, followed by 9 years of routine immunization of children aged 11 years. We used US age- and serogroup-specific surveillance data on incidence and mortality. Assumptions related to the impact of herd immunity were drawn from experience with routine meningococcal vaccination in the United Kingdom. We estimated costs per case, deaths prevented, life-years saved, and quality-adjusted life-years saved. With herd immunity, the catch-up and routine vaccination program for adolescents would prevent 8251 cases of meningococcal disease in a 10-year period (a 48% decrease). Excluding program costs, this catch-up and routine vaccination program would save US$551 million in direct costs and $920 million in indirect costs, including costs associated with permanent disability and premature death. At $83 per vaccinee, the catch-up vaccination would cost society approximately $223,000 per case averted, approximately $2.6 million per death prevented, approximately $127,000 per life-year saved, and approximately $88,000 per quality-adjusted life-year saved. Targeting counties with a high incidence of disease decreased the cost per life-year saved by two-thirds. Although costly, catch-up and routine vaccination of adolescents can have a

The First World War years of Sydney Domville Rowland: an early case of possible laboratory-acquired meningococcal disease.

PubMed

Wever, Peter C; Hodges, A J

2016-08-01

Sydney Domville Rowland was a bacteriologist and staff member at the Lister Institute of Preventive Medicine when the First World War broke out in 1914. Following a request to the Director of the Lister Institute to staff and equip a mobile field laboratory as quickly as possible, Rowland was appointed to take charge of No. 1 Mobile Laboratory and took up a temporary commission at the rank of Lieutenant in the Royal Army Medical Corps. On 9 October 1914, Rowland set out for the European mainland and was subsequently attached to General Headquarters in Saint-Omer, France (October 1914-June 1915), No. 10 Casualty Clearing Station in Lijssenthoek, Belgium (June 1915-February 1916, during which period he was promoted Major), and No. 26 General Hospital in Étaples, France (February 1916-March 1917). His research focused on gas gangrene, typhoid fever, trench fever, wound infection and cerebrospinal fever. In February of 1917, while engaged in identifying meningococcal carriers, Rowland contracted cerebrospinal meningitis to which he succumbed at age 44 on 6 March 1917. His untimely death might have been caused by laboratory-acquired meningococcal disease, especially since Rowland's work with Neisseria meningitidis isolates had extended beyond routine laboratory techniques and included risk procedures like immunisation of rabbits with pathogenic strains isolated from cerebrospinal fluid. Currently, microbiology laboratory workers who are routinely exposed to N. meningitidis isolates are recognised as a population at increased risk for meningococcal disease, for which reason recommended preventive measures include vaccination and handling of isolates within a class II biosafety cabinet. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash

PubMed Central

Carrol, E; Newland, P; Riordan, F; Thomson, A; Curtis, N; Hart, C

2002-01-01

Background: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. Aim: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. Methods: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07–15.9) versus 1.75 (0.19–14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Results: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS ≥8). Conclusions: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash. PMID:11919107

Meningococcal Photos

MedlinePlus

... Vaccine Campaign Podcast: Meningitis Immunization for Adolescents Meningitis Sepsis Meningococcal Photos Recommend on Facebook Tweet Share Compartir ... Vaccine Campaign Podcast: Meningitis Immunization for Adolescents Meningitis Sepsis File Formats Help: How do I view different ...

History of meningococcal vaccines and their serological correlates of protection.

PubMed

Vipond, Caroline; Care, Rory; Feavers, Ian M

2012-05-30

For over a hundred years Neisseria meningitidis has been known to be one of the major causes of bacterial meningitis. However, effective vaccines were not developed until the latter part of the 20th century. The first of these were based on purified high molecular weight capsular polysaccharides and more recently the development of glycoconjugate vaccines has made paediatric immunisation programmes possible. The prevention of group B meningococcal disease has remained a challenge throughout this period. This review charts the history of the development of meningococcal vaccines and the importance of serological correlates of protection in their evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Meningococcal Neonatal Purulent Conjunctivitis/Sepsis and Asymptomatic Carriage of N. meningitidis in Mother's Vagina and Both Parents' Nasopharynx.

PubMed

Chacon-Cruz, Enrique; Alvelais-Palacios, Jorge Arturo; Rodriguez-Valencia, Jaime Alfonso; Lopatynsky-Reyes, Erika Zoe; Volker-Soberanes, Maria Luisa; Rivas-Landeros, Rosa Maria

2017-01-01

Neonatal conjunctivitis is usually associated with vagina's infection by Chlamydia sp., N. gonorrhoeae , and/or other bacteria during delivery. Meningococcal neonatal conjunctivitis is an extremely rare disease. We report a case of neonatal meningococcal sepsis/conjunctivitis and asymptomatic carriage of N. meningitidis from both parents (vagina and nasopharynx). As part of our active surveillance for meningococcal disease at the Tijuana General Hospital (TGH), Mexico, we identified a 3-day-old newborn with meningococcal conjunctivitis and sepsis. The patient had a one-day history of conjunctivitis and poor feeding. Clinical examination confirmed profuse purulent conjunctival discharge, as well as clinical signs and laboratory findings suggestive of bacteraemia. Gram stain from conjunctival exudate revealed intracellular Gram negative diplococci; we presumed the baby had gonorrheal conjunctivitis; however, serogroup Y, N. meningitidis was isolated both from conjunctival exudate and blood. Additionally, isolation of serogroup Y, N. meningitidis was obtained from mother's vagina and both parents' nasopharynx. The baby was treated with 7 days of IV ceftriaxone and discharged with no sequelae.

Computational Analysis and Characterization of RC-135 External Aerodynamics

DTIC Science & Technology

2012-03-22

date date date AFIT/GAE/ENY/12-M06 Abstract Both the RC-135V/W Rivet Joint (RJ) and the RC-135U Combat Sent (CS) aircraft are United States Air...Page 1.1. RC-135V/W Rivet Joint [1] . . . . . . . . . . . . . . . . . . . . 2 1.2. RC-135U Combat Sent [1] . . . . . . . . . . . . . . . . . . . . . 2...1.3. RC-135V/W Rivet Joint BL9 antenna locations [2] . . . . . . . 3 1.4. RC-135U Combat Sent showing LCS with louver installed over exhaust [1

Suspected meningococcal meningitis on an aircraft carrier.

PubMed

Farr, Wesley; Gonzalez, Michele J; Garbauskas, Heather; Zinderman, Craig E; LaMar, James E

2004-09-01

A suspected case of meningococcal meningitis was diagnosed in a 24-year-old sailor onboard an aircraft carrier at sea in 2003. He was immediately confined to the ship's hospital ward under respiratory isolation precautions and was treated with intravenously administered antibiotics. His illness resolved without sequelae. A total of 99 close contacts from the ship were identified and given antibiotic prophylaxis, with directly observed therapy. British public health authorities were contacted to trace and treat persons identified as close contacts during a port call a few days before presentation. Managing a communicable disease such as meningococcal meningitis in the austere shipboard environment represents a unique challenge to military medical personnel. Successful management is possible through prompt treatment, respiratory isolation, and open communication between primary health care providers and public health officials. The identification of shipboard close contacts and other infection control procedures used by the ship's medical department are reviewed.

Rapid Response to a College Outbreak of Meningococcal Serogroup B Disease: Nation's First Widespread Use of Bivalent rLP2086 Vaccine

ERIC Educational Resources Information Center

Fiorito, Theresa M.; Bornschein, Suzanne; Mihalakos, Alysia; Kelleher, Catherine M.; Alexander-Scott, Nicole; Kanadanian, Koren V.; Raymond, Patricia; Sicard, Kenneth; Dennehy, Penelope H.

2017-01-01

Objective: To outline the reasoning behind use of bivalent rLP2086 in a Rhode Island college meningococcal B disease outbreak, highlighting the timeline from outbreak declaration to vaccination clinic, emphasizing that these two time points are <3 days apart. Participants: Staff, faculty, and students at College X eligible for vaccination.…

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV)

PubMed Central

Holst, Johan; Oster, Philipp; Arnold, Richard; Tatley, Michael V.; Næss, Lisbeth M.; Aaberge, Ingeborg S.; Galloway, Yvonne; McNicholas, Anne; O’Hallahan, Jane; Rosenqvist, Einar; Black, Steven

2013-01-01

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004–2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains. PMID:23857274

Meningitis - meningococcal

MedlinePlus

... of the head White blood cell (WBC) count Gram stain, other special stains Treatment Antibiotics will be started as soon as possible. Ceftriaxone is one of the most commonly used antibiotics. Penicillin in high doses is almost ... Meningococcal lesions on the back ...

Correlation of microstructure and low cycle fatigue properties for 13.5Cr1.1W0.3Ti ODS steel

NASA Astrophysics Data System (ADS)

He, P.; Klimenkov, M.; Möslang, A.; Lindau, R.; Seifert, H. J.

2014-12-01

Reduced activation oxide dispersion strengthened (ODS) steels are prospective structural materials for the blanket system and first wall components in Tokamak-type fusion reactors. Under the pulsed operation, these components will be predominantly subjected to cyclic thermal-mechanical loading which leads to inevitable fatigue damage. In this work, strain controlled isothermal fatigue tests were conducted for 13.5Cr1.1W0.3Ti ODS steel at 550 °C. The total strain range varied from 0.54% to 0.9%. After thermomechanical processing, 13.5CrWTi-ODS steel exhibits a remarkable lifetime extension with a factor of 10-20 for strain ranges Δε ⩽ 0.7%. 13.5Cr ODS steel shows no cyclic softening at all during the whole testing process irrespective of the strain range. TEM observations reveal ultrastable grain structure and constant dislocation densities around 1014 m-2, independent of the number of cycles or the applied strain amplitude. The presence of the stabilized ultrafine Y-Ti-O dispersoids enhances the microstructural stability and therefore leads to outstanding fatigue resistance for 13.5Cr1.1W0.3Ti-ODS steel.

Risk Factors for Serogroup C Meningococcal Disease during Outbreak among Men who Have Sex with Men, New York City, New York, USA.

PubMed

Ridpath, Alison; Greene, Sharon K; Robinson, Byron F; Weiss, Don

2015-08-01

Risk factors for illness during a serogroup C meningococcal disease outbreak among men who have sex with men in New York City, New York, USA, in 2012-2013 included methamphetamine and cocaine use and sexually transmitted infections. Outbreak investigations should consider routinely capturing information regarding drug use and sex-related risk factors.

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis

PubMed Central

Gasparini, Roberto; Landa, Paolo; Amicizia, Daniela; Icardi, Giancarlo; Ricciardi, Walter; de Waure, Chiara; Tanfani, Elena; Bonanni, Paolo; Lucioni, Carlo; Testi, Angela; Panatto, Donatella

2016-01-01

ABSTRACT The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable. PMID:27163398

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis.

PubMed

Gasparini, Roberto; Landa, Paolo; Amicizia, Daniela; Icardi, Giancarlo; Ricciardi, Walter; de Waure, Chiara; Tanfani, Elena; Bonanni, Paolo; Lucioni, Carlo; Testi, Angela; Panatto, Donatella

2016-08-02

The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.

Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?

PubMed

Rojahn, Astrid; Brusletto, Berit; Øvstebø, Reidun; Haug, Kari B F; Kierulf, Peter; Brandtzaeg, Petter

2008-09-01

To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes. Comparative, experimental study. University Hospital and laboratory. Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock. The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold. Although

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

PubMed

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable

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

PubMed

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

2017-06-29

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

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease.

PubMed

Hellenbrand, Wiebke; Koch, Judith; Harder, Thomas; Bogdan, Christian; Heininger, Ulrich; Tenenbaum, Tobias; Terhardt, Martin; Vogel, Ulrich; Wichmann, Ole; von Kries, Rüdiger

2015-11-01

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the

Immunogenicity and safety of an investigational quadrivalent meningococcal ACWY tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25 years of age.

PubMed

Baxter, Roger; Baine, Yaela; Ensor, Kathleen; Bianco, Veronique; Friedland, Leonard R; Miller, Jacqueline M

2011-03-01

An investigational quadrivalent Neisseria meningitidis serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) has been developed to expand available options for vaccination against invasive meningococcal disease. A total of 784 healthy adolescents and young adults 11 to 25 years of age were randomized (3:1) to receive a single dose of the MenACWY-TT vaccine or a licensed MenACWY diphtheria toxoid conjugate vaccine (MenACWY-DT). An additional nonrandomized group of 88 subjects 10 years of age received the MenACWY-TT vaccine only (MenACWY-TT/10). Immunogenicity was assessed 1 month postvaccination by human complement serum bactericidal assay (hSBA) for all serogroups. Solicited local and general symptoms were recorded for 8 days postvaccination and safety outcomes for 6 months. One month postvaccination, 81.9% to 96.1% of subjects had hSBA titers ≥ 1:8 in the MenACWY-TT group compared with 70.7% to 98.8% in the MenACWY-DT group. Exploratory analyses showed the proportion of subjects with hSBA titers ≥ 1:4 and ≥ 1:8 to be higher in the MenACWY-TT group than in the MenACWY-DT group for serogroups A, W-135, and Y. GMTs adjusted for age strata and baseline titer 1 month postvaccination were higher in the MenACWY-TT group than in the MenACWY-DT group for all 4 serogroups. The percentage of subjects reporting solicited local and general symptoms of any or Grade 3 severity or serious adverse events was similar between the 2 groups. Immune response and reactogenicity in the MenACWY-TT/10 group was similar to that in the MenACWY-TT group, except for higher hSBA-MenA GMTs in the MenACWY-TT/10 group. The investigational MenACWY-TT vaccine was immunogenic in adolescents and young adults, with an acceptable safety profile.

Invasive meningococcal disease in the Veneto region of Italy: a capture-recapture analysis for assessing the effectiveness of an integrated surveillance system.

PubMed

Baldovin, Tatjana; Lazzari, Roberta; Cocchio, Silvia; Furlan, Patrizia; Bertoncello, Chiara; Saia, Mario; Russo, Francesca; Baldo, Vincenzo

2017-05-02

Epidemiology of Neisseria meningitidis has been changing since the introduction of universal vaccination programmes against meningococcal serogroup C (MenC) and meningococcal serogroup B (MenB) has now become dominant. This study aimed to analyse the cases reported in institutional data recording systems to estimate the burden of invasive meningococcal diseases (IMDs) and assess the effectiveness of surveillance in Veneto region (Italy). Analysis was performed from 2007 to 2014 on data recorded in different systems: Mandatory Notification System, National Surveillance of Invasive Bacterial Diseases System and Laboratories Surveillance System (LSS), which were pooled into a combined surveillance system (CSS) and hospital discharge records (HDRs). A capture-recapture method was used and completeness of each source estimated. Number of cases with IMD by source of information and year, incidence of IMD by age group, case fatality rate (CFR) and distribution of meningococcal serogroups by year were also analysed. Combining the four data systems enabled the identification of 179 confirmed cases with IMD, achieving an overall sensitivity of 94.7% (95% CI: 90.8% to 98.8%), while it was 76.7% (95% CI: 73.6% to 80.1%) for CSS and 77.2% (95% CI: 74.1% to 80.6%) for HDRs. Typing of isolates was done in 80% of cases, and 95.2% of the typed cases were provided by LSS. Serogroup B was confirmed in 50.3% of cases. The estimated IMD notification rate (cases with IMD diagnosed and reported to the surveillance systems) was 0.48/100 000 population, and incidence peaked at 6.2/100 000 in children aged <1 year old (60.9% due to MenB), and increased slightly in the age group between 15 and 19 years (1.1/100 000). A CFR of 14% was recorded (8.7% in paediatric age). Quality of surveillance systems relies on case ascertainment based on serological characterisation of the circulating strains by microbiology laboratories. All available sources should be routinely combined to improve the

Use of Variable-Number Tandem Repeats To Examine Genetic Diversity of Neisseria meningitidis

PubMed Central

Yazdankhah, Siamak P.; Lindstedt, Bjørn-Arne; Caugant, Dominique A.

2005-01-01

Repetitive DNA motifs with potential variable-number tandem repeats (VNTR) were identified in the genome of Neisseria meningitidis and used to develop a typing method. A total of 146 meningococcal isolates recovered from carriers and patients were studied. These included 82 of the 107 N. meningitidis isolates previously used in the development of multilocus sequence typing (MLST), 45 isolates recovered from different counties in Norway in connection with local outbreaks, and 19 serogroup W135 isolates of sequence type 11 (ST-11), which were recovered in several parts of the world. The latter group comprised isolates related to the Hajj outbreak of 2000 and isolates recovered from outbreaks in Burkina Faso in 2001 and 2002. All isolates had been characterized previously by MLST or multilocus enzyme electrophoresis (MLEE). VNTR analysis showed that meningococcal isolates with similar MLST or MLEE types recovered from epidemiologically linked cases in a defined geographical area often presented similar VNTR patterns while isolates of the same MLST or MLEE types without an obvious epidemiological link showed variable VNTR patterns. Thus, VNTR analysis may be used for fine typing of meningococcal isolates after MLST or MLEE typing. The method might be especially valuable for differentiating among ST-11 strains, as shown by the VNTR analyses of serogroup W135 ST-11 meningococcal isolates recovered since the mid-1990s. PMID:15814988

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

PubMed Central

Bröker, Michael; Berti, Francesco; Costantino, Paolo

2016-01-01

ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

Multidisciplinary analysis of invasive meningococcal disease as a framework for continuous quality and safety improvement in regional Australia

PubMed Central

Taylor, Kathryn A; Durrheim, David N; Merritt, Tony; Massey, Peter; Ferguson, John; Ryan, Nick; Hullick, Carolyn

2018-01-01

Background System factors in a regional Australian health district contributed to avoidable care deviations from invasive meningococcal disease (IMD) management guidelines. Traditional root cause analysis (RCA) is not well-suited to IMD, focusing on individual cases rather than system improvements. As IMD requires complex care across healthcare silos, it presents an opportunity to explore and address system-based patient safety issues. Context Baseline assessment of IMD cases (2005–2006) identified inadequate triage, lack of senior clinician review, inconsistent vital sign recording and laboratory delays as common issues, resulting in antibiotic administration delays and inappropriate or premature discharge. Methods Clinical governance, in partnership with clinical and public health services, established a multidisciplinary Meningococcal Reference Group (MRG) to routinely review management of all IMD cases. The MRG comprised representatives from primary care, acute care, public health, laboratory medicine and clinical governance. Baseline data were compared with two subsequent evaluation points (2011–2012 and 2013–2015). Interventions Phase I involved multidisciplinary process mapping and development of a standardised audit tool from national IMD management guidelines. Phase II involved formalisation of group processes and advocacy for operational change. Phase III focused on dissemination of findings to clinicians and managers. Results Greatest care improvements were observed in the final evaluation. Median antibiotic delay decreased from 72 to 42 min and proportion of cases triaged appropriately improved from 38% to 75% between 2013 and 2015. Increasing fatal outcomes were attributed to the emergence of more virulent meningococcal serotypes. Conclusions The MRG was a key mechanism for identifying system gaps, advocating for change and enhancing communication and coordination across services. Employing IMD case review as a focus for district-level process

Meningococcal pneumonia in Japan: A case report and literature review.

PubMed

Hirai, Jun; Kinjo, Takeshi; Tome, Takaaki; Hagihara, Mao; Sakanashi, Daisuke; Nakamura, Hideta; Haranaga, Shusaku; Mikamo, Hiroshige; Fujita, Jiro

2016-12-01

Neisseria meningitidis often causes meningitis and meningococcemia; however, meningococcal pneumonia is quite rare. Herein, we report a case of non-invasive meningococcal pneumonia initially misdiagnosed as pneumonia due to Moraxella catarrhalis on the basis of a Gram stain in a 43-year-old woman with asthma, type 2 diabetes mellitus, and schizophrenia. She visited our hospital following a 3-day history of fever, productive cough, and shortness of breath. Since her sputum smear revealed Gram-negative diplococcus and the chest radiograph showed infiltration in the lower right lung field, her initial diagnosis was pneumonia caused by M. catarrhalis. However, the next day, the sputum culture colonies were unlike those of M. catarrhalis, and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed the pathogen to be N. meningitidis. As a result, we administered the appropriate treatment and ensured adequate infection prevention and control measures including, droplet precautions and prophylaxis provided to close contacts. Secondary infection did not occur. Although meningococcal pneumonia is not common, physicians should consider N. meningitidis when Gram-negative diplococci are observed in respiratory specimens, as N. meningitidis cannot be distinguished from M. catarrhalis with Gram staining alone. Moreover, it is also important to monitor the appearance of the pathogenic colonies and to closely coordinate with laboratory technicians to determine appropriate treatments. In this article, we review the previous case reports of meningococcal pneumonia reported in 1984-2015 in Japan, summarizing the clinical characteristics and comparing previous reviews of the literature. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[The meningococcal infection on Navy: modern clinical-and-epidemiological aspects].

PubMed

Makhnev, M V; Makhneva, I Iu

2004-10-01

The article presents the own data about modern clinical-and-epidemiological peculiarities of a meningococcal infection on Navy for 20 consecutive years (1982-2002) based on the analysis of the annual reports of fleet medical services and the inspection of 275 centers of a meningococcal infection in military troops. The centers with the single generalized form of a meningococcal infection prevailed. The centers with the number of people from 10 to 40 men amounted to 82%. The frequency of the meningococcal defeat of the people in the centers varied from 25% to 37% with the main role of meningococcae A. In the structure of a meningococcal infection the generalized forms amounted to 16%, located forms--25%, carriers--59%. In all regions the major form of the display of epidemic process in military collectives was seasonal sick rate. The article proved the electoral approach to the character and volume of curative-and-preventive measures.

Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

PubMed

Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

2016-06-17

MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Uptake of Meningococcal Vaccine in Arizona Schoolchildren After Implementation of School-Entry Immunization Requirements

PubMed Central

Hills, Rebecca A.; Allwes, Deborah; Rasmussen, Lisa

2013-01-01

Objectives Meningitis and bacteremia due to Neisseria meningitidis are rare but potentially deadly diseases that can be prevented with immunization. Beginning in 2008, Arizona school immunization requirements were amended to include immunization of children aged 11 years or older with meningococcal vaccine before entering the sixth grade. We describe patterns in meningococcal vaccine uptake surrounding these school-entry requirement changes in Arizona. Methods We used immunization records from the Arizona State Immunization Information System (ASIIS) to compare immunization rates in 11- and 12-year-olds. We used principal component analysis and hierarchical cluster analysis to identify and analyze demographic variables reported by the 2010 U.S. Census. Results Adolescent meningococcal immunization rates in Arizona increased after implementation of statewide school-entry immunization requirements. The increase in meningococcal vaccination rates among 11- and 12-year-olds from 2007 to 2008 was statistically significant (p<0.0001). All demographic groups had significantly higher odds of on-schedule vaccination after the school-entry requirement change (odds ratio range = 5.57 to 12.81, p<0.0001). County demographic factors that were associated with lower odds of on-schedule vaccination included higher poverty, more children younger than 18 years of age, fewer high school graduates, and a higher proportion of Native Americans. Conclusions This analysis suggests that implementation of school immunization requirements resulted in increased meningococcal vaccination rates in Arizona, with degree of response varying by demographic profile. ASIIS was useful for assessing changes in immunization rates over time. Further study is required to identify methods to control for population overestimates in registry data. PMID:23277658

Terminal Complement Blockade after Hematopoietic Stem Cell Transplantation Is Safe without Meningococcal Vaccination.

PubMed

Jodele, Sonata; Dandoy, Christopher E; Danziger-Isakov, Lara; Myers, Kasiani C; El-Bietar, Javier; Nelson, Adam; Wallace, Gregory; Teusink-Cross, Ashley; Davies, Stella M

2016-07-01

Eculizumab inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome and is now used as a first-line therapy in these diseases. Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of an increased risk of meningococcal infections in persons without adequate functional complement. Administration of meningococcal vaccine is required at least 2 weeks before administering the first dose of eculizumab, and this advice is included in the product label. Eculizumab use for treatment of TMA in hematopoietic stem cell transplantation (HSCT) recipients brings a significant dilemma regarding REMS required meningococcal vaccination. TMA after HSCT usually occurs within the first 100 days after transplantation when patients are severely immunocompromised and are not able to mount a response to vaccines. We evaluated 30 HSCT recipients treated with eculizumab for high-risk TMA without meningococcal vaccine. All patients received antimicrobial prophylaxis adequate for Neisseria meningitides during eculizumab therapy and for 8 weeks after discontinuation of the drug. Median time to TMA diagnosis was 28 days after transplant (range, 13.8 to 48.5). Study subjects received a median of 14 eculizumab doses (range, 2 to 38 doses) for HSCT-associated TMA therapy. There were no incidences of meningococcal infections. The incidences of bacterial and fungal bloodstream infections were similar in patients treated with eculizumab (n = 30) as compared with those with HSCT-associated TMA who did not receive any complement blocking therapy (n = 39). Our data indicate that terminal complement blockade in the early post-transplant period can be performed without meningococcal vaccination while using appropriate antimicrobial prophylaxis until complement

Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

PubMed Central

Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

2009-01-01

Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants

Laboratory-based surveillance of Neisseria meningitidis isolates from disease cases in Latin American and Caribbean countries, SIREVA II 2006-2010.

PubMed

Ibarz-Pavón, Ana Belén; Lemos, Ana Paula; Gorla, Maria Cecilia; Regueira, Mabel; Gabastou, Jean-Marc

2012-01-01

Published data on the epidemiology of meningococcal disease in Latin America and the Caribbean region is scarce and, when available, it is often published in Spanish and/or in non-peer-reviewed journals, making it difficult for the international scientific community to have access. Laboratory data on 4,735 Neisseria meningitidis strains was collected and reported by the National Reference Laboratories in 19 Latin American countries and the Caribbean Epidemiology Centre (CAREC) between 2006 and 2010 as part of the work carried out by the SIREVA II network. Serogroup and MIC to penicillin, rifampin and chloramphenicol were determined. Isolates were mainly obtained from patients <5 years, but each year around 25% of isolates came from adult patients. Serogroup distribution was highly variable among countries. Serogroup C was the main cause of disease in Brazil; the majority of disease seen in the Southern cone was caused by serogroup B, but serogroup W135 strains have increased in recent years. In the Andean and Mexico, Central America and Caribbean regions, serogroups B and C were equally present, and serogroup Y was frequently isolated. Isolates were generally susceptible to chloramphenicol, penicillin and rifampin, but almost 60% of isolates characterized in Southern cone countries presented intermediate resistance to penicillin. Five rifampin-resistant isolates have been isolated in Uruguay and Brazil. Serogroup distribution is highly variable among countries, but some geographic structuring can be inferred from these data. Epidemiological and laboratory data are scarce among Andean and Mexico, Central America and Caribbean countries. Evaluation and implementation of corrective measures on disease surveillance and reporting systems and the implementation of molecular diagnostic techniques and molecular characterization on meningococcal isolates are advised.

Meningococcal B Vaccination (4CMenB) in Infants and Toddlers

PubMed Central

Esposito, Susanna; Tagliabue, Claudia; Bosis, Samantha

2015-01-01

Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y) cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB). This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine. PMID:26351647

Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data

PubMed Central

Novak, Ryan T; Kambou, Jean Ludovic; Diomandé, Fabien V K; Tarbangdo, Tiga F; Ouédraogo-Traoré, Rasmata; Sangaré, Lassana; Lingani, Clement; Martin, Stacey W; Hatcher, Cynthia; Mayer, Leonard W; LaForce, F Marc; Avokey, Fenella; Djingarey, Mamoudou H; Messonnier, Nancy E; Tiendrébéogo, Sylvestre R; Clark, Thomas A

2016-01-01

Summary Background An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA–TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11.4 million people aged 1–29 years. We analysed national surveillance data around PsA–TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics. Methods We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA–TT implementation. We assessed the risk of meningitis disease and death between years. Findings During the 14 year period before PsA–TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0.29, 95% CI 0.28–0.30, p<0.0001) and a 64% decline in risk of fatal meningitis (0.36, 0.33–0.40, p<0.0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0.38, 95% CI 0.31–0.45, p<0.0001), and among children aged less than 1 year (54%, 0.46, 0.24–0.86, p=0.02) and people aged 30 years and older (55%, 0.45, 0.22–0.91, p=0.003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory

Persistence of the immune response two years after vaccination with quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in Asian adolescents.

PubMed

Quiambao, Beatriz P; Jain, Hermant; Bavdekar, Ashish; Dubey, Anand Prakash; Kolhe, Devayani; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M

2016-08-02

Invasive meningococcal disease is a serious infection that is most often vaccine-preventable. Long-term protection relies on antibody persistence. Here we report the persistence of the immune response 2 y post-vaccination with a quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT) compared with a MenACWY polysaccharide vaccine (Men-PS), in Asian adolescents aged 11-17 y. We also report a re-analysis of data from the primary vaccination study. This persistence study (NCT00974363) conducted in India and the Philippines included subjects who previously (study NCT00464815) received a single dose of MenACWY-TT or Men-PS. Persistence of functional antibodies was measured in 407 MenACWY-TT recipients and 132 Men-PS recipients (according-to-protocol cohort) using a rabbit complement serum bactericidal assay (rSBA, cut-off 1:8). Vaccine-related serious adverse events (SAEs) occurring since the end of the initial vaccination study were retrospectively recorded. Two y post-vaccination ≥99.3% of adolescents who received MenACWY-TT had persisting antibody titers ≥1:8 against each vaccine serogroup. Antibody persistence was higher (exploratory analysis) in the MenACWY-TT group than the Men-PS group in terms of rSBA titers ≥1:8 for serogroups W and Y; rSBA titers ≥1:128 for serogroups A, W and Y; and rSBA GMTs for serogroups A, W and Y; and was lower in the MenACWY-TT group for rSBA GMTs for serogroup C. No vaccine-related SAEs were reported. The results of this study indicated that antibodies persisted for at least 2 y in the majority of adolescents after vaccination with a single dose of MenACWY-TT.

ASTRONAUT YOUNG, JOHN W. - ZERO-GRAVITY (ZERO-G) - KC-135

NASA Image and Video Library

1978-12-15

S79-30347 (31 March 1979) --- Taking advantage of a brief period of zero-gravity afforded aboard a KC-135 flying a parabolic curve, the flight crew of the first space shuttle orbital flight test (STS-1) goes through a spacesuit donning exercise. Astronaut John W. Young has just entered the hard-material torso of the shuttle spacesuit by approaching it from below. He is assisted by astronaut Robert L. Crippen. The torso is held in place by a special stand here, simulating the function provided by the airlock wall aboard the actual shuttle craft. The life support system is mated to the torso on Earth and remains so during the flight, requiring this type of donning and doffing exercise. Note Crippen?s suit is the type to be used for intravehicular activity in the shirt sleeve environment to be afforded aboard shuttle. The suit worn by Young is for extravehicular activity (EVA). Young will be STS-1 commander and Crippen, pilot. They will man the space shuttle orbiter 102 Columbia. Photo credit: NASA

[Results of intensive therapy of meningococcal sepsis in children].

PubMed

Gujanica, Z; Janković, I; Jevtić, D; Marković, M; Marjanović, B; Janković, B

2001-01-01

The authors report on the method, course and results of treatment of patients with meningococcal septicaemia. The two most common forms of meningococcal disease are meningococcal septicaemia (MS) and meningitis. Severe MS is a fulminant form of sepsis characterized by a rapidly spreading purpuric rash, haemodynamic instability and rapid progression to shock or death. The diganosis of MS was confirmed by isolation of NM in blood or cerebrospinal fluid, and/or positive solubile bacterial antigenes. However, in some children whose symptoms were consistent in MS (temperature and extensive purpura), no bacterial or soluble antigens were detected, particularly when they had been previours antibiotic treatment. Several scoring systems have been used to predict morbidity and mortility from MS. We selected the prognostic scor developed by Malley et al. Absolute neutrophil count less than 3 x 10(3)/mm3, platelet count less than 150 x 10(3)/mm3 and poor perfusion are indicators of poor prognosis. The presence of at least two of these indicators was associated with an 82% of risk of death. We reviewed the hospital records of 36 paediatric patients with acute meningococcal infection during a 5-year period. The age of our patients ranged from 2 months to 15 years (mean 4.4 yrs). Twenty seven (70%) of 36 children had MS and 11 (40.7%) had both MS and meningitis. Based on Malley scor, 13 (48.1%) patients had at least two predictors with > 82% of risk of lethal outcome. Four children (30.7%) died. Severe MS was diagnosed in 16 (59.2%) patients, who required mechanical ventilation (16; 59.2%), or continuous inotropic support and invasive measures of circulatory parametars (15; 55.5%). Shock treatment consisted of large volumes of crystalloid or colloid infusions thad ranged from 140 to 500 ml/kg/24 hrs (mean 215 ml/kg) Our results indicate that early controlled mechanical ventilations increase safety of large volume infusion with continuous invasive monitoring and inotropic

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

PubMed Central

Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M

2015-01-01

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885] PMID:25969894

Pathology in rabbits treated with leukocyte-degraded meningococci in combination with meningococcal endotoxin.

PubMed Central

DeVoe, I W; Gilka, F; Gilchrist, J E; Yu, E

1977-01-01

The effects of a preparative dose of the leukocyte egesta containing degraded meningococci and a provocative dose of the meningococcal lipopolysaccharide on development of pathological lesions associated with disseminated intravascular coagulation were studied in tissues of 32 rabbits. These effects were compared with effects of a single dose of meningococcal lipopolysaccharide as well as leukocyte egesta containing degraded Staphylococcus epidermidis. Rabbits injected subcutaneously with egesta containing degraded meningococci followed after 12 h with meningococcal endotoxin (intravenously) exhibited heterophilic leukocytosis and disseminated intravascular coagulation mainly in the pulmonary capillaries and venules; focal necroses occurred in myocardium, lungs, and liver, whereas, cortical renal necrosis developed in lethal cases. Similar lesions, however, but less severe and with less frequency, developed even after a single dose of meningococcal endotoxin or after endotoxin that followed a dose of supernatant fluid from normal leukocytes. Our findings suggest that meningococcal material from polymorphonuclear degradation plays a role in the pathology characteristic of meningococcal septicemia. Images PMID:406202

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

PubMed

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

2014-01-04

meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères. Copyright © 2014 Daugla et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

[Meningococcal infections associated with febrile purpura among children hospitalized in a Moroccan Hospital: incidence and associated clinical factors].

PubMed

Gueddari, Widad; Sabri, Hayat; Chabah, Meryem

2017-01-01

Febrile purpura (FP) is suggestive of meningococcal disease, requiring almost always further investigations and a treatment based on broad spectrum antibiotics. This study aimed to determine the incidence of meningococcal infections as well as their associated clinical signs in children with febrile purpura hospitalized in the emergency department. We conducted a descriptive, retrospective study in the pediatric emergency department at the Children's Hospital of Casablanca over a period of 3 years. The hospitalized children with FP who had undergone bloodculture, whether or not associated with lumbar puncture, were included in the study. Statistical analysis was performed using SPSS v.16 software. We enrolled 96 children, 49 boys and 47 girls. The average age was 53.3 ± 40.5 months. Mean body temperature was 38.9°C. Meningococcal infection was diagnosed in 35/96 children. The diagnosis of meningococcemia was retained in 22 children, associated with meningitis in four patients. Symptoms and physical signs significantly associated with meningococcal infection included lethargy (p = 0.04), convulsions (p = 0.01) and purpura occurring outside the skin area drained by the superior vena cava (p = 0.01). FP occurring outside the skin area drained by the superior vena cava or associated with convulsions is srongly related to meningococcal infection, whose incidence seems to be high among Moroccan children.

Antibodies for Rickettsia spp. in patients with negative serology for dengue virus, leptospirosis, and meningococcal disease in municipalities of São Paulo State, Brazil.

PubMed

Prata, Juliana Anacleto Cabral; Souza, Celso Eduardo de; Angerami, Rodrigo Nogueira; Barbosa, Taíse Marongio Cotrim de Moraes; Santos, Fabiana Cristina Pereira Dos; Colombo, Silvia; Guercio, Vânia Martins Fontes Del; Donalísio, Maria Rita

2016-01-01

Brazilian spotted fever is an infectious disease with a high mortality rate if not treated early. Differential diagnosis is difficult, as the first clinical signs are non-specific and can be confused with other diseases. The aim of the study was to investigate evidence of infection with Rickettsia rickettsii and Rickettsia parkeri in negative sera samples, collected in 2014, from patients with suspected leptospirosis, dengue fever, and meningococcal disease in Atibaia and Bragança Paulista municipalities of the State of São Paulo. The samples stored at the Institute Adolfo Lutz in Campinas were tested using an indirect immunofluorescence assay (IFA) with IgG and IgM against R. rickettsii and R. parkeri. Real-time polymerase chain reaction (PCR) testing was performed for the sera samples of patients who died (n = 3), those with initial suspicion of meningococcal disease (n = 6), and those with positive IFA results. Of 258 samples from Bragança Paulista, 4 (1.6%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. Of 155 samples from Atibaia, 2 (1.3%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. No sample showed positive PCR results. This serological investigation suggests there is evidence of exposure to Rickettsia spp. in residents of areas that have environmental conditions favorable to the spread of bacteria, in which Brazilian spotted fever incidence was not previously confirmed.

Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

PubMed

Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

2009-12-01

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada.

PubMed

Delea, Thomas E; Weycker, Derek; Atwood, Mark; Neame, Dion; Alvarez, Fabián P; Forget, Evelyn; Langley, Joanne M; Chit, Ayman

2017-01-01

Public health programs to prevent invasive meningococcal disease (IMD) with monovalent serogroup C meningococcal conjugate vaccine (MCV-C) and quadrivalent meningococcal conjugate vaccines (MCV-4) in infancy and adolescence vary across Canadian provinces. This study evaluated the cost-effectiveness of various vaccination strategies against IMD using current and anticipated future pricing and recent epidemiology. A cohort model was developed to estimate the clinical burden and costs (CAN$2014) of IMD in the Canadian population over a 100-year time horizon for three strategies: (1) MCV-C in infants and adolescents (MCV-C/C); (2) MCV-C in infants and MCV-4 in adolescents (MCV-C/4); and (3) MCV-4 in infants (2 doses) and adolescents (MCV-4/4). The source for IMD incidence was Canadian surveillance data. The effectiveness of MCV-C was based on published literature. The effectiveness of MCV-4 against all vaccination regimens was assumed to be the same as for MCV-C regimens against serogroup C. Herd effects were estimated by calibration to estimates reported in prior analyses. Costs were from published sources. Vaccines prices were projected to decline over time reflecting historical procurement trends. Over the modeling horizon there are a projected 11,438 IMD cases and 1,195 IMD deaths with MCV-C/C; expected total costs are $597.5 million. MCV-C/4 is projected to reduce cases of IMD by 1,826 (16%) and IMD deaths by 161 (13%). Vaccination costs are increased by $32 million but direct and indirect IMD costs are projected to be reduced by $46 million. MCV-C/4 is therefore dominant vs. MCV-C/C in the base case. Cost-effectiveness of MCV-4/4 was $111,286 per QALY gained versus MCV-C/4 (2575/206 IMD cases/deaths prevented; incremental costs $68 million). If historical trends in Canadian vaccines prices continue, use of MCV-4 instead of MCV-C in adolescents may be cost-effective. From an economic perspective, switching to MCV-4 as the adolescent booster should be considered.

Long-term persistence of protective antibodies in Dutch adolescents following a meningococcal serogroup C tetanus booster vaccination.

PubMed

van Ravenhorst, Mariëtte B; Marinovic, Axel Bonacic; van der Klis, Fiona R M; van Rooijen, Debbie M; van Maurik, Marjan; Stoof, Susanne P; Sanders, Elisabeth A M; Berbers, Guy A M

2016-12-07

Due to waning immunity, infant vaccination with meningococcal serogroup C conjugated (MenCC) vaccines is insufficient to maintain long-term individual protection. Adolescent booster vaccination is thought to offer direct protection against invasive meningococcal disease (IMD) but also to reduce meningococcal carriage and transmission and in this way establish herd protection in the population. Previously, we studied antibody levels after adolescent MenCC booster vaccination. In the present study, the adolescent vaccinees were revisited after three years to determine antibody persistence and to predict long-term protection. Meningococcal serogroup C tetanus toxoid conjugated (MenC-TT) vaccine was administered to 10-, 12- and 15-year old participants who had been primed nine years earlier with a single dose of MenC-TT vaccine. Blood samples were collected before, 1month, 1year and 3years after the adolescent booster vaccination. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (rSBA). Meningococcal serogroup C polysaccharide and tetanus toxoid specific antibody levels were measured using fluorescent-bead-based multiplex immunoassay. Long-term protection was estimated using longitudinal multilevel antibody decay modeling. Of the original 268 participants, 201 (75%) were revisited after 3years. All participants still had an rSBA titer above the protective threshold of ⩾8 and 98% ⩾128. The 15-year-olds showed the highest antibody titers. Using a bi-exponential decay model, the median time to fall below the protection threshold (rSBA titer <8) was 16.3years, 45.9years and around 270years following the booster for the 10-, 12- and 15-year-olds, respectively. After a first steep decline in antibody levels in the first year after the booster, antibody levels slowly declined between one and three years post-booster. A routine MenC-TT booster vaccination for adolescents in the Netherlands will likely provide long

Fast tracking the vaccine licensure process to control an epidemic of serogroup B meningococcal disease in New Zealand.

PubMed

Lennon, Diana; Jackson, Catherine; Wong, Sharon; Horsfall, Maraekura; Stewart, Joanna; Reid, Stewart

2009-08-15

Epidemics of serogroup B meningococcal disease are rare. Strain-specific outer membrane vesicle vaccines, which are not marketed, are the only current tool for control. A correlate of protection is ill defined, but published data suggest that measured serum bactericidal antibody levels parallel efficacy. Even infants can mount a strain-specific antibody response to a strain-specific vaccine. New Zealand's epidemic (1991-2007; peak rate [in 2001], 17.4 cases per 100,000 persons) was dominated by a single strain. After a 5-year search (1996-2001) for a manufacturer for a strain-specific outer membrane vesicle vaccine, a fast-tracked research program (2002-2004) determined the safety and immunogenicity of vaccine in infants (2 age groups: 6-10 weeks and 6-8 months), children (age, 16-24 months), and school-aged children (age, 8-12 years) after an adult trial. The vaccine was reactogenic, compared with control vaccines (meningococcal C conjugate and routine infant vaccines), but retention was high. Three vaccine doses produced antibody levels (measured by serum bactericidal assay) that were considered to be adequate for public health intervention. However, in young infants, a fourth dose was required to achieve levels equivalent to those achieved by other age groups. Provisional licensure by New Zealand's MedSafe was based on serological criteria strengthened by bridged safety data from studies of the parent outer membrane vesicle vaccine, independent assessment of manufacturing quality, and a clear plan for safety monitoring and effectiveness evaluation after licensure.

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015.

PubMed

Kretz, Cecilia B; Retchless, Adam C; Sidikou, Fati; Issaka, Bassira; Ousmane, Sani; Schwartz, Stephanie; Tate, Ashley H; Pana, Assimawè; Njanpop-Lafourcade, Berthe-Marie; Nzeyimana, Innocent; Nse, Ricardo Obama; Deghmane, Ala-Eddine; Hong, Eva; Brynildsrud, Ola Brønstad; Novak, Ryan T; Meyer, Sarah A; Oukem-Boyer, Odile Ouwe Missi; Ronveaux, Olivier; Caugant, Dominique A; Taha, Muhamed-Kheir; Wang, Xin

2016-10-01

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013-2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.

Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock.

PubMed

Hellum, Marit; Øvstebø, Reidun; Brusletto, Berit S; Berg, Jens P; Brandtzaeg, Petter; Henriksson, Carola E

2014-03-01

The plasma level of bacterial lipopolysaccharides (LPS) is associated with activation of the coagulation system, inhibition of fibrinolysis and the nature of the clinical presentation and outcome in patients with meningococcal disease. Tissue factor (TF)-bearing microparticles (MPs) appear to contribute to the pathogenesis of disseminated intravascular coagulation (DIC). The aim of this study was to investigate the relationship between MP-associated TF activity and the level of bacterial LPS in plasma from patients with meningococcal septic shock and meningitis. MPs isolated from citrated plasmas were assessed for TF-dependent activity with both a plasma-based thrombin generation assay (CAT) and whole blood-based thromboelastometry (ROTEM). The LPS level was measured using a chromogenic Limulus amebocyte lysate assay. MPs obtained from patients with meningococcal septic shock initiated significantly more efficient and TF-dependent thrombin generation in the CAT assay compared to MPs from patients with meningococcal meningitis. Differences in MP-associated TF activity between the septic shock patients and the meningitis patients were also evident when MPs were added to whole blood using ROTEM. The level of plasma LPS in patients with septic shock (range 2-2,100 EU/mL) was correlated with thrombogram parameters in the CAT assay; lagtime (r(s)=-0.84), time to peak (rs=-0.83), peak (r(s)=0.85) and ETP (r(s)=0.83). MPs obtained from patients with meningococcal septic shock displayed more efficient TF-dependent thrombin generation and clot formation compared to MPs from meningitis patients. MP-associated TF activity was closely associated with plasma LPS levels in the septic shock group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

PubMed Central

Andreae, Clio A.; Sessions, Richard B.; Virji, Mumtaz

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis. PMID:29547646

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design.

PubMed

Andreae, Clio A; Sessions, Richard B; Virji, Mumtaz; Hill, Darryl J

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

Meningococcal Vaccine (For Parents)

MedlinePlus

... are 11 or 12 years old, with a booster given at age 16 for teens 13–18 ... the ages of 13–15 should get a booster dose between the ages of 16–18. Teens ... those entering the military) won't need a booster dose. A full series of the meningococcal conjugate ...

Meningococcal Two-Partner Secretion Systems and Their Association with Outcome in Patients with Meningitis

PubMed Central

Piet, Jurgen R.; van Ulsen, Peter; ur Rahman, Sadeeq; Bovenkerk, Sandra; Bentley, Stephen D.

2016-01-01

Two-partner secretion (TPS) systems export large TpsA proteins to the surface and extracellular milieu. In meningococci, three different TPS systems exist, and of these, TPS system 2 (TPS2) and TPS3 can be detected by the host's immune system. We evaluated the distribution of TPS systems among clinical isolates from two prospective cohort studies comprising 373 patients with meningococcal meningitis. TPS system 1 was present in 91% of isolates, and system 2 and/or 3 was present in 67%. The TPS system distribution was related to clonal complexes. Infection with strains with TPS2 and/or TPS3 resulted in less severe disease and better outcomes than infection with strains without these systems. Using whole-blood stimulation experiments, we found no differences in the host cytokine response between patients infected with TPS system 2 and 3 knockout strains and patients infected with a wild-type strain. In conclusion, meningococcal TPS system 2 and/or 3 is associated with disease severity and outcome in patients with meningitis. PMID:27324486

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

PubMed

Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

2014-01-01

Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

Why are U.S. girls getting meningococcal but not human papilloma virus vaccines? Comparison of factors associated with human papilloma virus and meningococcal vaccination among adolescent girls 2008 to 2012.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Silliman, Rebecca A; Clark, Jack A; Hanchate, Amresh

2015-01-01

Human papilloma virus (HPV) vaccination rates in the United States remain low, compared with other recommended adolescent vaccines. We compared factors associated with intention to receive and receipt of HPV and meningococcal vaccines and completion of the HPV vaccine series among U.S. adolescent girls. Secondary analysis of data from the National Immunization Survey-Teen for 2008 through 2012 was performed. Multivariable logistic modeling was used to determine factors associated with intent to receive and receipt of HPV and meningococcal vaccination, completion of the HPV vaccine series among girls who started the series, and receipt of HPV vaccination among girls who received meningococcal vaccination. Provider recommendation increased the odds of receipt and intention to receive both HPV and meningococcal vaccines. Provider recommendation was also associated with a three-fold increase in HPV vaccination among girls who received meningococcal vaccination (p<.001), indicating a relationship between provider recommendation and missed vaccine opportunities. However, White girls were 10% more likely to report provider recommendation than Black or Hispanic girls (p<.01), yet did not have higher vaccination rates, implying a role for parental refusal. No factors predicted consistently the completion of the HPV vaccine series among those who started. Improving provider recommendation for co-administration of HPV and meningococcal vaccines would reduce missed opportunities for initiating the HPV vaccine series. However, different interventions may be necessary to improve series completion. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

[Clinical-pathogenetic features of meningococcal infection in children].

PubMed

Buriak, V N; Serhyenko, A S

2011-01-01

Analysis features of clinical manifestation and pathogenetic mechanisms of development of meningococcal infection is introduced. It is emphasized that in most cases mentioned infection is characterized by mild course as nasopharyngitidis. However relatively seldom developing generalize form put this phatology on third place after intestinal infections and septicemia in structure of child mortality from infection deseases. Occurence of generalize forms of meningococcal infection depend on peculiarity of immune response is followed by release of endotoxin and exotoxin in blood stream. This toxins start up pathogenetic mechanisms, which lead to toxic shock, adrenal glands hemorrhage, brain edema, brain stem wedge in big occipital foramen.

UK parents’ attitudes towards meningococcal group B (MenB) vaccination: a qualitative analysis

PubMed Central

Jackson, Cath; Yarwood, Joanne; Saliba, Vanessa

2017-01-01

Objectives (1) To explore existing knowledge of, and attitudes, to group B meningococcal disease and serogroup B meningococcal (MenB) vaccine among parents of young children. (2) To seek views on their information needs. Design Cross-sectional qualitative study using individual and group interviews conducted in February and March 2015, prior to the introduction of MenB vaccine (Bexsero) into the UK childhood immunisation schedule. Setting Community centres, mother and toddler groups, parents’ homes and workplaces in London and Yorkshire. Participants 60 parents of children under 2 years of age recruited via mother and baby groups and via an advert posted to a midwife-led Facebook group. Results Although recognising the severity of meningitis and septicaemia, parents’ knowledge of group B meningococcal disease and MenB vaccine was poor. While nervous about fever, most said they would take their child for MenB vaccination despite its link to fever. Most parents had liquid paracetamol at home. Many were willing to administer it after MenB vaccination as a preventive measure, although some had concerns. There were mixed views on the acceptability of four vaccinations at the 12-month booster visit; some preferred one visit, while others favoured spreading the vaccines over two visits. Parents were clear on the information they required before attending the immunisation appointment. Conclusions The successful implementation of the MenB vaccination programme depends on its acceptance by parents. In view of parents’ recognition of the severity of meningitis and septicaemia, and successful introduction of other vaccines to prevent bacterial meningitis and septicaemia, the MenB vaccination programme is likely to be successful. However, the need for additional injections, the likelihood of post-immunisation fever and its management are issues about which parents will need information and reassurance from healthcare professionals. Public Health England has developed

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

PubMed

Lee, Hoan Jong; Chung, Moon-Hyun; Kim, Woo Joo; Hong, Young Jin; Choi, Kyong Min; Lee, Jina; Oh, Chi Eun; Welsch, Jo Anne; Kim, Kyung-Hyo; Hong, Ki Bae; Dagnew, Alemnew F; Bock, Hans; Dull, Peter M; Odrljin, Tatjana

2014-11-01

This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

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

PubMed

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

2016-12-20

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

[Epidemiological characteristics of meningococcal meningitis in Guangxi Zhuang Autonomous Region during 1996 and 2007].

PubMed

Lin, Mei; Dong, Bai-Qing; Yang, Jin-Ye

2009-02-01

To analyze the epidemiological characteristics of meningococcal meningitis and provide evidences for disease control. The method of descriptive epidemiology has been used to analyze the data collected. A total of 419 cases were reported with meningococcal meningitis between 1996-2007, annual incidence rate was 0.07/100,000. 68 cases were dead and mortatity was 16.23% . Highly sporadic distribution by areas was observed in the cases reported. And the incidence peak was between January and April. The aged was mainly at 0-9 years There was trace that the incidence move to aged at 10 19 years old in recent years. The in-cidence rate was higher in male than that in female. And it was mainly attacked in peasants, students and children left-behined at home. Outbreaks had occasionally occurred in Guangxi. The first outbreak caused by Neisseria meningitidis group C in China was reported. The strains isola-ted mainly were with Neisseria meningitidis group A, which accounting for 61.53% of the strains,followed by group C(15. 38%)and Group B (7.69%). Group A was found to be 100% re-sistant to SMZ-TMP,and both group C and B were 100% resistant to sulfanilamide. 1.28% the prevalence of carrier was confirmed by the throat swabs. The positive rate of titer to group A and C were 29. 95o and 21. 720 respectively, and the mean titers were 4.57 microg/ml and 1.70 microg/ml re-spectively. The characteristics of Meningococcal meningitis are summarized as low incidence,high mortabity,highly sporadic distribution, grouping diversity and increasing incidence in older population. Comprehensive measures with the priority of vaccination is the key measure for meningococcal meningitis control.

Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

2015-01-01

Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection.

PubMed

Bergman, Peter; Johansson, Linda; Wan, Hong; Jones, Allison; Gallo, Richard L; Gudmundsson, Gudmundur H; Hökfelt, Tomas; Jonsson, Ann-Beth; Agerberth, Birgitta

2006-12-01

Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.

Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection▿

PubMed Central

Bergman, Peter; Johansson, Linda; Wan, Hong; Jones, Allison; Gallo, Richard L.; Gudmundsson, Gudmundur H.; Hökfelt, Tomas; Jonsson, Ann-Beth; Agerberth, Birgitta

2006-01-01

Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP. PMID:17030578

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

PubMed Central

Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

2014-01-01

Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

Invasive meningococcal disease--improving management through structured review of cases in the Hunter New England area, Australia.

PubMed

Guimont, Chantal; Hullick, Carolyn; Durrheim, David; Ryan, Nick; Ferguson, John; Massey, Peter

2010-03-01

Invasive meningococcal disease (IMD) is the most common infectious cause of death in childhood in developed countries. This disease may cause severe disability or death if a patient is sub-optimally managed. An audit was performed in Australia of all 2005-06 notified IMD cases to elicit correctable issues. Over the 2 year period, 24 cases were notified in the Hunter New England Health area. These cases were reviewed by an expert panel to highlight key correctable issues in recognition and management of IMD. The 24 patients were aged between 1 month and 70 years. Thirteen (54%) were children and 14 (58%) were women. Six (25%) cases developed complications, two being severe (one death, one limb amputations). These patients had risk factors for IMD. The emergency department average delay between assessment and administration of antibiotics was 57.8 min. There were avoidable factors identified in both patients with a poor outcome. Length of delay in initiating antibiotic therapy has been associated with poor outcome, thus the delay in our series is of concern. The audit highlighted many potentially correctable issues in the medical, laboratory and public health management of IMD cases.

The missing link: family physician perspectives on barriers and enablers to prescribing a new Meningococcal B vaccine and other recommended, non-government funded vaccines.

PubMed

Taylor, Kathryn A; Stocks, Nigel; Marshall, Helen S

2014-07-16

To determine factors influencing Family Physician (FP) uptake of non government-funded vaccines, and to explore FP attitudes towards the introduction and use of a new vaccine to protect against serogroup B meningococcal disease to inform its future introduction into the Australian Immunisation Schedule. Quantitative, self-administered state-wide questionnaire mailed to all FPs in South Australia (n=1786). Results from 523 FP respondents in South Australia, collected between June and October 2013. Self-reported immunisation counselling practices; and knowledge, attitudes and barriers to prescribing of Meningococcal B (Men B) vaccine and other recommended, non-funded immunisations. The response rate was 30% (n=523). While most (59%) respondents had worked in general practice for over 20 years, only 39% of all respondents had ever had personal or professional experience with a case of invasive meningococcal disease (IMD). Most FPs (63%) were aware that a meningococcal B vaccine was being developed, and 93% of respondents agreed that this vaccine should be government-funded. FPs ranked Men B vaccine as the highest priority to receive funding of eight currently non-funded immunisation strategies. High vaccine cost and low patient socioeconomic status were identified as definite barriers to prescribing non-funded vaccines by 59% of respondents. Past IMD experience significantly affected attitudes and prescribing practices. IMD, while encountered rarely in clinical practice, is considered an important disease to vaccinate against by FPs. Cost and perceived low socioeconomic status of patients are substantial barriers to FPs prescribing Men B and other non-funded vaccines, and inclusion of such vaccines on the National Immunisation Program is likely to improve equity of access. Copyright © 2014 Elsevier Ltd. All rights reserved.

A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

PubMed

Eerkens, Jelmer W; Nichols, Ruth V; Murray, Gemma G R; Perez, Katherine; Murga, Engel; Kaijankoski, Phil; Rosenthal, Jeffrey S; Engbring, Laurel; Shapiro, Beth

2018-05-25

Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans. Copyright © 2018 Elsevier Inc. All rights reserved.

Pulmonary edema in meningococcal septicemia associated with reduced epithelial chloride transport.

PubMed

Eisenhut, Michael; Wallace, Helen; Barton, Paul; Gaillard, Erol; Newland, Paul; Diver, Michael; Southern, Kevin W

2006-03-01

To test the hypothesis that meningococcal septicemia-related pulmonary edema is associated with a systemic abnormality of epithelial sodium and chloride transport and to investigate an association with hormones regulating Na transport. Prospective observational study. The 24-bed pediatric intensive care unit and pediatric wards of Royal Liverpool Children's Hospital. Consecutive children admitted to the pediatric intensive care unit and pediatric wards with a diagnosis of meningococcal septicemia and children (controls) with noninfectious critical illness receiving ventilatory support in the pediatric intensive care unit. We measured sweat and saliva electrolytes, renal electrolyte excretion, nasal potential difference, and aldosterone, thyroxine, and cortisol levels. Pulmonary edema was diagnosed by chest radiography and its severity quantified by calculation of ventilation index at admission and duration of mechanical ventilation. We recruited 17 patients with severe meningococcal septicemia (nine patients with pulmonary edema), 14 patients with mild meningococcal septicemia, and 20 controls. Sweat and saliva Na and Cl concentrations and renal Na excretion were significantly (p < .05) higher in patients with pulmonary edema compared with controls. Nasal potential difference and amiloride response in patients with pulmonary edema were not significantly different to controls, but response to a low Cl solution was reduced in the nasal airway of patients with pulmonary edema (p < .05). Sweat and saliva chloride concentrations correlated significantly and better with ventilation index and duration of ventilation than sodium concentrations. Aldosterone, thyroxine, and cortisol levels were not significantly different between groups. We have confirmed that meningococcal septicemia-related pulmonary edema is associated with reduced systemic sodium and chloride transport. Features of reduced Cl transport were most closely associated with markers of respiratory compromise

Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer

PubMed Central

Brehony, Carina; O'Connor, Lois; Meyler, Kenneth; Jolley, Keith A.; Bray, James; Bennett, Desiree; Maiden, Martin C. J.; Cunney, Robert

2016-01-01

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates. PMID:27629899

The introduction of the meningococcal B (MenB) vaccine (Bexsero®) into the national infant immunisation programme--New challenges for public health.

PubMed

Ladhani, Shamez N; Campbell, Helen; Parikh, Sydel R; Saliba, Vanessa; Borrow, Ray; Ramsay, Mary

2015-12-01

The United Kingdom is the first country to introduce Bexsero(®) (GSK Biologicals), a multicomponent, protein-based vaccine against meningococcal group B (MenB), into the national infant immunisation programme. This vaccine is like no other licensed vaccine and poses a number of implementation and surveillance challenges in England. From 01 September 2015, UK infants were offered a reduced two dose primary immunisation schedule at 2 and 4 months followed by a booster at 12 months. Because of high rates of fever post-vaccination, parents were advised to give their infants three doses of prophylactic paracetamol, with the first dose given as soon as possible after the primary MenB vaccination dose. Since the vaccine only protects against 73-88% of MenB strains causing invasive disease in England, clinical isolates and PCR-positive samples will require extensive characterisation by the Meningococcal Reference Unit (MRU) at Public Health England (PHE) in order to monitor vaccine effectiveness and identify potential vaccine failures. PHE is also conducting detailed clinical and epidemiological surveillance to assess the impact of the MenB immunisation programme on the morbidity and mortality associated with invasive meningococcal disease in infants and young children. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Epidemiological evidence for the role of the haemoglobin receptor, HmbR, in meningococcal virulence

PubMed Central

Harrison, Odile B.; Evans, Nicholas J.; Blair, Jessica M.; Grimes, Holly S.; Tinsley, Colin R.; Nassif, Xavier; Kriz, Paula; Ure, Roisin; Gray, Steve J.; Derrick, Jeremy P.; Maiden, Martin C.J.; Feavers, Ian M.

2009-01-01

The distribution of the haemoglobin receptor gene (hmbR) was investigated in disease and carried Neisseria meningitidis isolates revealing that the gene occurred at a significantly higher frequency in disease isolates compared to those obtained from carriage. Where hmbR was absent, the locus was occupied by the cassettes exl2 or exl3, or with a “pseudo hmbR” gene designated exl4. The hmbR locus in published N. meningitidis genomes, as well as N. gonorrhoeae and N. lactamica ST-640, exhibited characteristics of a pathogenicity island. These data are consistent with a role for the hmbR gene in meningococcal disease. PMID:19476432

Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines▿

PubMed Central

Sandbu, Synne; Feiring, Berit; Oster, Philipp; Helland, Oddveig S.; Bakke, Hilde S. W.; Næss, Lisbeth M.; Aase, Audun; Aaberge, Ingeborg S.; Kristoffersen, Anne-Cathrine; Rydland, Kjersti M.; Tilman, Sandrine; Nøkleby, Hanne; Rosenqvist, Einar

2007-01-01

MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 μg), MeNZB (25 μg), or the MenBvac and MeNZB (doses of 12.5 μg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of ≥4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries. PMID:17634513

The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.

PubMed

Yaesoubi, Reza; Trotter, Caroline; Colijn, Caroline; Yaesoubi, Maziar; Colombini, Anaïs; Resch, Stephen; Kristiansen, Paul A; LaForce, F Marc; Cohen, Ted

2018-01-01

The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all

Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

PubMed

Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-09-08

MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was <1:4, or at least a fourfold higher hSBA titre than baseline if the prevaccination titre was ≥1:4), percentages of subjects with serum bactericidal activity (hSBA) ≥1:8 for serogroups A, C, W and Y and hSBA geometric mean titres (GMTs). Local and systemic reactions and all adverse events (AEs) were recorded for 7 days, and medically attended AEs for 1 month post-vaccination. Seroresponse rates after MenACWY-CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006.

PubMed

McNicholas, Anne; Galloway, Yvonne; Stehr-Green, Paul; Reid, Stewart; Radke, Sarah; Sexton, Kerry; Kieft, Charlotte; Macdonald, Claire; Neutze, Jocelyn; Drake, Ross; Isaac, Dorothy; O'Donnell, Mary; Tatley, Michael; Oster, Philipp; O'Hallahan, Jane

2007-01-01

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.

Meningococcal Education: More than Just a Vaccine

ERIC Educational Resources Information Center

Kuenzi, Lana

2004-01-01

The administration of meningitis vaccinations to the college population has recently been the topic of much discussion. Much of the controversy has surrounded the promotion of widespread vaccinations or educational campaigns about the vaccine for incoming freshman students. Recommendations about the use of meningococcal vaccines for college…

Bacterial agents causing meningitis during 2013-2014 in Turkey: A multi-center hospital-based prospective surveillance study.

PubMed

Ceyhan, Mehmet; Ozsurekci, Yasemin; Gürler, Nezahat; Karadag Oncel, Eda; Camcioglu, Yıldız; Salman, Nuran; Celik, Melda; Emiroglu, Melike Keser; Akin, Fatih; Tezer, Hasan; Parlakay, Aslinur Ozkaya; Tuygun, Nilden; Tamburaci, Diyar; Dinleyici, Ener Cagri; Karbuz, Adem; Uluca, Ünal; Alhan, Emre; Çay, Ümmühan; Kurugol, Zafer; Hatipoğlu, Nevin; Şiraneci, Rengin; İnce, Tolga; Sensoy, Gülnar; Belet, Nursen; Coskun, Enes; Yilmaz, Fatih; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Celik, Ümit; Ozen, Metehan; Akaslan, Aybüke; Devrim, İlker; Kuyucu, Necdet; Öz, Fatmanur; Bozdemir, Sefika Elmas; Kara, Ahu

2016-11-01

This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.

46 CFR 7.135 - Point Sur, CA to Cape Blanco, OR.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Pacific Coast § 7.135 Point Sur, CA to Cape Blanco, OR. (a) A line drawn from Monterey Harbor Light “6” to latitude 36°36.5′ N. longitude 121°53.2′ W. (Monterey Harbor Anchorage Buoy “A”); thence to the... 46 Shipping 1 2010-10-01 2010-10-01 false Point Sur, CA to Cape Blanco, OR. 7.135 Section 7.135...

46 CFR 7.135 - Point Sur, CA to Cape Blanco, OR.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Pacific Coast § 7.135 Point Sur, CA to Cape Blanco, OR. (a) A line drawn from Monterey Harbor Light “6” to latitude 36°36.5′ N. longitude 121°53.2′ W. (Monterey Harbor Anchorage Buoy “A”); thence to the... 46 Shipping 1 2014-10-01 2014-10-01 false Point Sur, CA to Cape Blanco, OR. 7.135 Section 7.135...

46 CFR 7.135 - Point Sur, CA to Cape Blanco, OR.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Pacific Coast § 7.135 Point Sur, CA to Cape Blanco, OR. (a) A line drawn from Monterey Harbor Light “6” to latitude 36°36.5′ N. longitude 121°53.2′ W. (Monterey Harbor Anchorage Buoy “A”); thence to the... 46 Shipping 1 2013-10-01 2013-10-01 false Point Sur, CA to Cape Blanco, OR. 7.135 Section 7.135...

46 CFR 7.135 - Point Sur, CA to Cape Blanco, OR.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Pacific Coast § 7.135 Point Sur, CA to Cape Blanco, OR. (a) A line drawn from Monterey Harbor Light “6” to latitude 36°36.5′ N. longitude 121°53.2′ W. (Monterey Harbor Anchorage Buoy “A”); thence to the... 46 Shipping 1 2012-10-01 2012-10-01 false Point Sur, CA to Cape Blanco, OR. 7.135 Section 7.135...

Risk factors for invasive meningococcal disease in southern Queensland, 2000-2001.

PubMed

McCall, B J; Neill, A S; Young, M M

2004-08-01

The aim of this paper is to describe the risk factors for invasive meningococcal disease (IMD) in southern Queensland. A case control study during the calendar years 2000-2001 was undertaken. Eighty-four laboratory-confirmed cases of IMD were notified. Four patients died and were excluded from the present study. Sixty-two (78%) eligible cases and 79 controls selected from the same age group and medical practice as cases, were interviewed. Univariate analysis found that IMD was associated with sharing bedrooms with two or more people (odds ratio (OR) 4.3; 95% confidence interval (CI) 1.2-17.0, P = 0.01), any exposure to tobacco smoke (smoker or passive exposure; OR 2.3; 95% CI 1.1-4.8, P = 0.02), passive exposure to tobacco smoke (OR 2.4; 95% CI 1.0-5.6, P = 0.03) and recent upper respiratory tract infection (OR 1.9, 95% CI 0.9-4.1, P = 0.06). Children who were breast-fed were less likely to develop IMD (OR 0.3; 95% CI 0.1-1.1, P = 0.04). Attendance at a childcare centre was not associated with an increased risk of IMD. In multivariate analysis, IMD was associated with children under 6 years of age who shared a bedroom with two or more people (OR 7.4; 95% CI 1.5-36.1, P = 0.01) or who had a primary carer who smoked (OR 9.1; 95% CI 2.1-39.9, P = 0.003). This is the second Australian study that identifies links between risk of IMD and exposure to cigarette smoke. The risk of IMD in young children could be further reduced if primary caregivers did not smoke. This information may contribute a new perspective to antismoking campaigns.

Safety of Quadrivalent Meningococcal Conjugate Vaccine in Children 2-10 Years.

PubMed

Tartof, Sara Yee; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Solano, Zendi; Jacobsen, Steven J; Tseng, Hung-Fu

2017-11-01

Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK, Siena, Italy) was approved for children 2-10 years of age in the United States. Although no safety concerns arose from clinical trials, it remains important to monitor its safety in routine clinical settings. Kaiser Permanente Southern California members 2-10 years old who received MenACWY-CRM between September 2011 and September 2014 were included. Electronic health records were searched using a validated algorithm to identify 26 prespecified events of interests (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to 1 year after MenACWY-CRM vaccination. SMAEs were categorized by International Classification of Diseases, 9th revision diagnostic categories. All events were reviewed to confirm the diagnosis and symptom onset date. The study was descriptive (NCT01452438); no statistical tests were performed. Among 387 vaccinated children, 327 with ≥6 months membership before vaccination were analyzed. Among EOIs, 9 asthma cases and 1 myasthenia gravis case underwent chart review which confirmed 1 incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly because of unrelated injury and poisoning. The remaining events occurred sporadically after vaccination and most were unlikely related to vaccination based on medical record review. One incident EOI of asthma late in the 1-year observation period and sporadic distribution of SMAEs were observed. These data do not suggest safety concerns associated with MenACWY-CRM vaccination in children 2-10 years old.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

PubMed

Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

[Vaccination against meningococcal B disease. Public statement of the Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP)].

PubMed

Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2015-03-01

Meningococcal invasive disease, including the main clinical presentation forms (sepsis and meningitis), is a severe and potentially lethal infection caused by different serogroups of Neisseria meningitidis. Meningococcal serogroup B is the most prevalent in Europe. Most cases occur in children, with a mortality rate of 10% and a risk of permanent sequelae of 20-30% among survivors. The highest incidence and case fatality rates are observed in healthy children under 2-3 years old, followed by adolescents, although it can occur at any age. With the arrival in Spain of the only available vaccine against meningococcus B, the Advisory Committee on Vaccines of the Spanish Association of Paediatrics has analysed its preventive potential in detail, as well as its peculiar administrative situation in Spain. The purpose of this document is to publish the statement of the Committee as regards this vaccination and the access to it by the Spanish population, taking into account that it has been only authorized for people at risk. The vaccine is available free in the rest of Europe for those who want to acquire it, and in some countries and regions it has been introduced into the systematic immunisation schedules. The Committee considers that Bexsero® has a profile of a vaccine to be included in the official schedules of all the Spanish autonomous communities and insists on the need for it to be available in pharmacies for its administration in all children older than 2 months. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

PubMed

Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María Del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L; Salas, Antonio

2016-11-02

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10 -8 ) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10 -9 ). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10 -8 ). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

PubMed

McGill, F; Heyderman, R S; Michael, B D; Defres, S; Beeching, N J; Borrow, R; Glennie, L; Gaillemin, O; Wyncoll, D; Kaczmarski, E; Nadel, S; Thwaites, G; Cohen, J; Davies, N W S; Miller, A; Rhodes, A; Read, R C; Solomon, T

2016-04-01

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunogenicity of the meningococcal polysaccharide conjugate vaccine in pediatric kidney transplant patients.

PubMed

Nelson, Delphine R; Fadrowski, Jeffrey; Neu, Alicia

2018-06-01

Immunosuppressed kidney transplant patients may have suboptimal response to vaccinations. The aim of this study was to determine antibody response to a quadrivalent meningococcal conjugate vaccine (MenACWY-D) in adolescents with a kidney transplant. This was a prospective, single-center, cohort study. Adolescent patients (11-22 years old) with a functioning kidney transplant for at least 3 months and no previous meningococcal vaccination were eligible for enrollment. Antibody levels to all serogroups were measured before vaccination (baseline) and at 4 weeks and 1, 2 and 3 years after vaccination. Seropositivity was defined as a titer ≥ 1:8 at baseline, and seroconversion as a fourfold or greater increase in antibody titer from baseline at 4 weeks post-vaccination. Geometric mean titers (GMTs) were calculated at each time point and compared to published GMTs from vaccinated healthy adolescents. Nineteen patients were enrolled. No patient had seroprotective titers against all four serogroups at baseline. At 4 weeks post-vaccination 41% of patients seroconverted to all four serogroups, with seroconversion rates of 88, 53, 71 and 94% for serogroups A, C, W and Y, respectively. GMTs were significantly lower in adolescents with a kidney transplant than in healthy adolescents at 1 month (p = 0.02) and 3 years (p = 0.04) post-vaccination. There were no significant adverse events, episodes of rejection or death in any patient. Adolescents with a kidney transplant may not respond adequately to MenACWY-D and may experience more rapid declines in antibody titers than healthy adolescents. Further study is needed to determine if alternative dosing schedules can improve antibody response in this population.

Meningococcal meningitis group A: a successful control of an outbreak by mass vaccination.

PubMed

Bushra, H E; Mawlawi, M Y; Fontaine, R E; Afif, H

1995-11-01

Jeddah is the main point of entry to the holy places in Saudi Arabia. An outbreak of meningococcal disease (MCD) occurred during the fasting lunar month for Muslims, Ramadan (March-April) of 1992. To assess the threat of local spread of MCD within Jeddah, the effects of previous and a mass vaccination programme against MCD during the outbreak, we reviewed the medical records of confirmed cases (CC) of MCD (defined as a bacteriologically confirmed case or a case diagnosed by latex test) and their vaccination status in the last five years before the outbreak. There were 41 CC of meningitis due to Neisseria meningitidis (group A). The ratio of males to females was 4.1:1. Thirty two percent of the cases were religious visitors. About one fourth (22%) of the cases were Pakistani. More than half (57%) of the cases, who were residents of Jeddah, lived in the north-eastern part of the city, as did half of the Pakistani cases. The case-fatality rate among CC was 19.5%. Persons who visited the Makkah (Mecca) during Ramadan were more likely to get the disease than those who did not (odds ratio [OR] = 6.1; 95% confidence interval [CI] 1.4-40.7). Unvaccinated persons were more likely to get the disease than those who were vaccinated against MCD (OR = 13.9; 95% CI 1.8-296). Meningococcal vaccine (MCV) against MCD was effective in preventing the disease. However, MCV was of no protective value if it had been administered more than five years before the outbreak. The reason mentioned most frequently for not being vaccinated by both cases (84%) and controls (57%) was lack of knowledge about the disease. Health education programmes should be strengthened and promoted. A good collaborative surveillance system between Jeddah and other holy cities, especially Makkah, is needed to abort outbreaks among religious visitors and to prevent the spread of MCD outbreaks.

Maternal and perinatal factors associated with subsequent meningococcal, Haemophilus or enteroviral meningitis in children: database study.

PubMed

Goldacre, M J; Wotton, C J; Maisonneuve, J J

2014-02-01

We used a database of 248 659 births, with follow-up to subsequent disease, in the Oxford record linkage archive (1979-1999) to study the influence of family, maternal, and perinatal factors on subsequent hospital admission for meningococcal, Haemophilus, and enteroviral meningitis in the children. In this summary, we report key findings that were significant in multivariate analysis. Meningococcal meningitis was significantly associated with maternal smoking [odds ratio (OR) 2·1, 95% confidence interval (CI) 1·2-3·7]. Haemophilus meningitis was associated with having older siblings (e.g. second child compared to first-born, OR 3·3, 95% CI 2·0-5·6). Enteroviral meningitis was associated with low birth weight (OR 2·2, 95% CI 1·3-3·6) and male sex (OR 1·7, 95% CI 1·2-2·3). The mothers of six of the 312 children with enteroviral meningitis had previously had enteroviral meningitis themselves. We concluded that several maternal characteristics influence the risk of these types of meningitis.

Safety and immunogenicity of an investigational meningococcal ACWY conjugate vaccine (MenACWY-CRM) in healthy Indian subjects aged 2 to 75 years.

PubMed

Lalwani, Sanjay; Agarkhedkar, Sharad; Gogtay, Nithya; Palkar, Sonali; Agarkhedkar, Shalaka; Thatte, Urmila; Vakil, Hoshang; Jonnalagedda, Rekha; Pedotti, Paola; Hoyle, Margaret; Bhusal, Chiranjiwi; Arora, Ashwani

2015-09-01

This phase 3, multi-center, open-label study evaluated the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo(®); Novartis Vaccines and Diagnostics S.r.l., Siena, Italy) in healthy Indian subjects aged 2-75 years, to provide data for licensure in India. A total of 180 subjects were enrolled (60 subjects 2-10 years, 60 subjects 11-18 years, and 60 subjects 19-75 years) and received one dose of MenACWY-CRM. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination. Adverse events were collected throughout the 29-day study period. Percentages of subjects with post-vaccination hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively. Geometric mean titers rose 7-fold to 42-fold against the four serogroups. Similar immune responses were observed for the age subgroups 2-10 years, 11-18 years, and 19-75 years. Seroresponse rates at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively. The vaccine was well tolerated with no safety concerns. A single dose of MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated in an Indian population 2-75 years of age. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Building 1204, oblique view to west, 135 mm lens. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Building 1204, oblique view to west, 135 mm lens. - Travis Air Force Base, Squadron Operations & Readiness Crew Facility, W Street, Armed Forces Special Weapons Project Q Area, Fairfield, Solano County, CA

KC-135 Survivability in a War in Europe

DTIC Science & Technology

1989-05-01

IIESEARCHlRPR KC-135 SURVIVA~BILITY IN4 A WA~R IN EUROPE 6T COL joHN EKWALL 3.989c ei-.T ..... , t =T’ p \\47 MR JIVERSI~r UAIRE s’rAT AIR FORCE ...MAWEIJL AIR FORCE BASbAB AIR WAR COLLEGE AIR UNIVERSITY KC-135 SURVIVABILITY IN A WAR IN EUROPE by John Ekwall Lieutenant Colonel, USAF A DEFENSE...ANALYTICAL STUDY SUBMITTED TO THE FACULTY IN FULLFILLMENT OF THE CURRICULUM REQUIREMENT Advisor: Colonel Frank W. Anderson, Jr. MAXWELL AIR FORCE BASE

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

PubMed

O'Connor, L; Ward, M; Bennett, D; Mulhall, R; O'Lorcain, P; Cunney, R; McDermott, R; Neville, E; Heslin, J; FitzGerald, R; Meyler, K; Conlon, M; Clarke, A; Corcoran, B; Fitzpatrick, G; O'Connor, B; Flanagan, P; O'Flanagan, D; Cotter, S

2015-05-28

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7–2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

Building 931, oblique view to southeast, 135 mm lens. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Building 931, oblique view to southeast, 135 mm lens. - Travis Air Force Base, Central Battery Charging Building, North of W Street, Armed Forces Special Weapons Project Q Area, Fairfield, Solano County, CA

Human Lipooligosaccharide IGG That Prevents Endemic Meningococcal Disease Recognizes an Internal Lacto-N-neotetraose Structure*

PubMed Central

Cheng, Hui; Yang, Zhijie; Estabrook, Michele M.; John, Constance M.; Jarvis, Gary A.; McLaughlin, Stephanie; Griffiss, J. McLeod

2011-01-01

Antibodies that initiate complement-mediated killing of Neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. Human IgGs that bind the neisserial L7 lipooligosaccharide (LOS) are bactericidal for L3,7 and L2,4 meningococci in the presence of human complement. These strains share a lacto-N-neotetraose (nLc4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc4 α chain to characterize further the binding and bactericidal activity of nLc4 LOS IgG. We found that the nLc4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc4 (non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc3 α chain that lacks this Gal residue. IgG that bound the internal nLc3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc4 terminal Gal residue for binding killed L2,4 stains but not L3,7 strains. These results show that the diversity of LOS antibodies in human serum is as much a function of the conformation of multiple antigens by a single glycoform as of the production of multiple glycoforms. Differences in sensitivity to killing by human nLc4 LOS IgG may account for the fact that fully two-thirds of endemic group B meningococcal disease in infants and children is caused by L3,7 strains, but only 20% is caused by L2,4 stains. PMID:22027827

Building 904, oblique view to southeast, 135 mm lens. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Building 904, oblique view to southeast, 135 mm lens. - Travis Air Force Base, Base Spares Warehouse No. 1, Dixon Avenue & W Street, Armed Forces Special Weapons Project Q Area, Fairfield, Solano County, CA

Building 904, oblique view to northwest, 135 mm lens ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Building 904, oblique view to northwest, 135 mm lens - Travis Air Force Base, Base Spares Warehouse No. 1, Dixon Avenue & W Street, Armed Forces Special Weapons Project Q Area, Fairfield, Solano County, CA

Prediction of meningococcal meningitis epidemics in western Africa by using climate information

NASA Astrophysics Data System (ADS)

YAKA, D. P.; Sultan, B.; Tarbangdo, F.; Thiaw, W. M.

2013-12-01

The variations of certain climatic parameters and the degradation of ecosystems, can affect human's health by influencing the transmission, the spatiotemporal repartition and the intensity of infectious diseases. It is mainly the case of meningococcal meningitis (MCM) whose epidemics occur particularly in Sahelo-Soudanian climatic area of Western Africa under quite particular climatic conditions. Meningococcal Meningitis (MCM) is a contagious infection disease due to the bacteria Neisseria meningitis. MCM epidemics occur worldwide but the highest incidence is observed in the "meningitis belt" of sub-Saharan Africa, stretching from Senegal to Ethiopia. In spite of standards, strategies of prevention and control of MCS epidemic from World Health Organization (WHO) and States, African Sahelo-Soudanian countries remain frequently afflicted by disastrous epidemics. In fact, each year, during the dry season (February-April), 25 to 250 thousands of cases are observed. Children under 15 are particularly affected. Among favourable conditions for the resurgence and dispersion of the disease, climatic conditions may be important inducing seasonal fluctuations in disease incidence and contributing to explain the spatial pattern of the disease roughly circumscribed to the ecological Sahelo-Sudanian band. In this study, we tried to analyse the relationships between climatic factors, ecosystems degradation and MCM for a better understanding of MCM epidemic dynamic and their prediction. We have shown that MCM epidemics, whether at the regional, national or local level, occur in a specific period of the year, mainly from January to May characterised by a dry, hot and sandy weather. We have identified both in situ (meteorological synoptic stations) and satellitales climatic variables (NCEP reanalysis dataset) whose seasonal variability is dominating in MCM seasonal transmission. Statistical analysis have measured the links between seasonal variation of certain climatic parameters

Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.

PubMed

Schlesinger, M; Nave, Z; Levy, Y; Slater, P E; Fishelson, Z

1990-09-01

High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.

Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) Neisseria meningitidis clone in the African meningitis belt.

PubMed

Lamelas, Araceli; Hauser, Julia; Dangy, Jean-Pierre; Hamid, Abdul-Wahab M; Röltgen, Katharina; Abdul Sater, Mohamad R; Hodgson, Abraham; Sie, Ali; Junghanss, Thomas; Harris, Simon R; Parkhill, Julian; Bentley, Stephen D; Pluschke, Gerd

2017-08-01

Countries of the African 'meningitis belt' are susceptible to meningococcal meningitis outbreaks. While in the past major epidemics have been primarily caused by serogroup A meningococci, W strains are currently responsible for most of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the first time in 2002, with the first meningitis cases caused by these bacteria reported in 2003. Here we describe results of a comparative whole-genome analysis of 74 W:ST-2881 strains isolated within the framework of two longitudinal colonization and disease studies conducted in Ghana and Burkina Faso. Genomic data indicate that the W:ST-2881 clone has emerged from Y:ST-175(CC175) bacteria by capsule switching. The circulating W:ST-2881 populations were composed of a variety of closely related but distinct genomic variants with no systematic differences between colonization and disease isolates. Two distinct and geographically clustered phylogenetic clonal variants were identified in Burkina Faso and a third in Ghana. On the basis of the presence or absence of 17 recombination fragments, the Ghanaian variant could be differentiated into five clusters. All 25 Ghanaian disease isolates clustered together with 23 out of 40 Ghanaian isolates associated with carriage within one cluster, indicating that W:ST-2881 clusters differ in virulence. More than half of the genes affected by horizontal gene transfer encoded proteins of the 'cell envelope' and the 'transport/binding protein' categories, which indicates that exchange of non-capsular antigens plays an important role in immune evasion.

Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa.

PubMed

Brynildsrud, Ola Brønstad; Eldholm, Vegard; Bohlin, Jon; Uadiale, Kennedy; Obaro, Stephen; Caugant, Dominique A

2018-05-22

In the African meningitis belt, a region of sub-Saharan Africa comprising 22 countries from Senegal in the west to Ethiopia in the east, large epidemics of serogroup A meningococcal meningitis have occurred periodically. After gradual introduction from 2010 of mass vaccination with a monovalent meningococcal A conjugate vaccine, serogroup A epidemics have been eliminated. Starting in 2013, the northwestern part of Nigeria has been affected by yearly outbreaks of meningitis caused by a novel strain of serogroup C Neisseria meningitidis (NmC). In 2015, the strain spread to the neighboring country Niger, where it caused a severe epidemic. Following a relative calm in 2016, the largest ever recorded epidemic of NmC broke out in Nigeria in 2017. Here, we describe the recent evolution of this new outbreak strain and show how the acquisition of capsule genes and virulence factors by a strain previously circulating asymptomatically in the African population led to the emergence of a virulent pathogen. This study illustrates the power of long-read whole-genome sequencing, combined with Illumina sequencing, for high-resolution epidemiological investigations. Copyright © 2018 the Author(s). Published by PNAS.

Investigation Into The Needs of Part 135 Operators to Access Airports Restricted Under FAR Part 135 Sections 135.213, 135.219 and/or 135.225

NASA Technical Reports Server (NTRS)

Eckert, Clifford A.; Stough, H. P. (Technical Monitor)

2002-01-01

NASA and the FAA have joint interests and responsibilities for developing guidelines and standards for cockpit displays of Flight Information Services (FIS) information and for developing enhancements to the planned FAA Data Link (FISDL) services. NASA and the FAA have established responsibilities in connection with development tasks for enhancements to the FISDL project. This report is the result of NASA Task 2, "Weather Support Concept- Part 135 Operations." The objective of the task was to determine the needs of Part 135 operators as they relate to FAA Part 135 Sections 135.213, 135.219 and 135.225, which pertain to weather reporting requirements at destination airports. This report discusses the results of two questionnaires completed by volunteer Part 135 operators that questioned their operations, their needs for flying to airports without weather reporting compatibilities, and suggestions for modifying FARs 135.213, 135.219 and 135.225. The operators pointed out airports in areas of the CONUS that were needed for IFR operations but lacked weather reporting capabilities and they offered practical suggestions for changes to the FARs. Related to operators's needs, and discussed in this report, were the Fractional Ownership NPRM and the possible impact of GPS WAAS and LAAS approaches.

Meningococcal serogroup C immunogenicity, antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine: A randomized controlled trial.

PubMed

van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Knol, Mirjam J; Stoof, Susanne P; Sanders, Elisabeth A M; Berbers, Guy A M

2017-08-24

Adolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster. Healthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year. Of 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds. Both MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease

Priming for immunologic memory in adults by meningococcal group C conjugate vaccination.

PubMed

Vu, David M; de Boer, Alberdina W; Danzig, Lisa; Santos, George; Canty, Bridget; Flores, Betty M; Granoff, Dan M

2006-06-01

Meningococcal group C polysaccharide-protein conjugate vaccines (MCV) prime infants and children for memory anticapsular responses upon subsequent exposure to unconjugated polysaccharide. The objective of this study was to determine whether MCV primes vaccine-naïve adults and adults previously vaccinated with meningococcal polysaccharide vaccine (MPSV) for memory antibody responses. Meningococcal vaccine-naïve adults were randomized to receive either MCV (MCV/naïve group) (n = 35) or pneumococcal conjugate vaccine (PCV) (PCV/naïve group) (n = 34). Participants with a history of receiving MPSV were given MCV (MCV/MPSV group) (n = 26). All subjects were challenged 10 months later with one-fifth of the usual dose of MPSV (10 mug of each polysaccharide). Sera were obtained before the conjugate vaccination and before and 7 days after the MPSV challenge and assayed for immunoglobulin G (IgG) anticapsular antibody concentrations and bactericidal titers. The MCV/naïve group had 7- to 10-fold-higher serum IgG and bactericidal responses after the MPSV challenge than the PCV/naïve group (P < 0.001). The increases (n-fold) in anticapsular antibody concentrations in the MCV/naïve group were greatest in subjects with antibody concentrations of 2 microg/ml before the challenge; P < 0.0001). Only 3 of 11 MCV-vaccinated subjects who had received MPSV before enrollment and who had antibody concentrations of meningococcal vaccine-naïve adults primes for robust memory antibody responses. There was no evidence of induction of memory by MCV in adults previously vaccinated with MPSV.

Genotypic and Phenotypic Characterization of Carriage and Invasive Disease Isolates of Neisseria meningitidis in Finland

PubMed Central

Saukkoriipi, Annika; Bratcher, Holly B.; Bloigu, Aini; Juvonen, Raija; Silvennoinen-Kassinen, Sylvi; Peitso, Ari; Harju, Terttu; Vainio, Olli; Kuusi, Markku; Maiden, Martin C. J.; Leinonen, Maija; Käyhty, Helena; Toropainen, Maija

2012-01-01

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates. PMID:22135261

Assessment of immune response to meningococcal disease: comparison of a whole-blood assay and the serum bactericidal assay.

PubMed

Ison, C A; Anwar, N; Cole, M J; Galassini, R; Heyderman, R S; Klein, N J; West, J; Pollard, A J; Morley, S; Levin and the Meningococcal, R e

1999-10-01

A whole-blood assay (WBA), which assesses the complete bactericidal activity of blood, was compared with the serum bactericidal assay (SBA), which measures antibody and complement mediated cell lysis. Twenty children infected with serogroup B strains and 25 infected with serogroup C strains were studied 8-12 weeks after disease, and 29 healthy children were used as controls. The infecting strain (convalescent children only) and two reference strains, MC58 (B:15:P1.7, 16) and NCTC 8554 (C:NT:P1.5) were used. In children previously infected with a serogroup B strain, bactericidal activity was detected in 95% and 85% to their infecting strain by the WBA (>50% killing) and the SBA (s), respectively. Bactericidal activity to the reference serogroup B and C strain was detected by WBA in 70 and 75% of children, respectively, and the SBA in 45% and 20%. In contrast bactericidal activity was detected to both serogroup C strains in >80% of children previously infected with a serogroup C strain using either assay and in 48% (WBA) and 20% (SBA) to the reference serogroup B strain. Levels of bactericidal activity were detectable in fewer control children. Children convalescing from meningococcal disease develop an immune response to their infecting strain, detectable by both the WBA and SBA, which is independent of age. However, the WBA appears to be a more sensitive measure of bactericidal activity to heterologous strains than the SBA. Copyright 1999 Academic Press.

Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.

PubMed

Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray

2015-06-26

Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624. Crown

Throat Culture from Patients with Meningococcal Meningitis

DTIC Science & Technology

1990-01-01

THROAT CULTURE FROM PATIENTS-’WITH MENINGOCOCCAL MENINGITIS BY J.E. Sippel and N.I. Girigs U.S. NAVAL MEDICAL RESEARCH UNIT NO. 3 (CAIRO, ARAB REPUBLIC...lowv albumin eoncen rations, characteristically, have a centra fpit and are throat swabs from teenage or young dults but that it als’q underestimites...8217described would’/cletzrly facilitate recognition read at 590 tim against commensal staphylococci and strep - NP IIRENWALD The procedure is linear t thie

Atypical clinical presentation of meningococcal meningitis: a case report.

PubMed

Izzo, Ilaria; Pileri, Paola; Merello, Maria; Gnesin, Paolo; Cogi, Enrico; Aggiusti, Carlo; Giacomelli, Laura; Ettori, Stefano; Colombini, Paolo; Collidá, Andrea

2016-09-01

A young woman was examined in the Emergency Department for fever, pharyngitis and widespread petechial rash. Physical examination, including neurological evaluation, did not show any other abnormalities. Chest X-ray was negative. Blood exams showed leukocytosis and CPR 20 mg/dL (nv<0.5 mg/dL). On the basis of these results and petechial rash evidence, lumbar puncture was performed. CSF was opalescent; physico-chemical examination showed: total proteins 2.8 (nv 0.15-0.45), glucose 5 (nv 59-80), WBC 7600/μL (nv 0-4/ μL). In the hypothesis of meningococcal meningitis, antimicrobial therapy was started. Blood and cerebrospinal fluid cultures were positive for N. meningitidis. During the first hours the patient experienced hallucinations and mild psychomotor agitation, making a spontaneous recovery. A brain MRI showed minimal extra-axial inflammatory exudates. She was discharged after 10 days in good condition. We underline the need to consider meningococcal meningitis diagnosis when any suggestive symptom or sign is present, even in the absence of the classic meningitis triad, to obtain earlier diagnosis and an improved prognosis.

Prevalence of meningococcal carriage in children and adolescents aged 10-19 years in Chile in 2013.

PubMed

Díaz, Janepsy; Cárcamo, Marcela; Seoane, Mabel; Pidal, Paola; Cavada, Gabriel; Puentes, Rodrigo; Terrazas, Solana; Araya, Pamela; Ibarz-Pavon, Ana B; Manríquez, Macarena; Hormazábal, Juan C; Ayala, Salvador; Valenzuela, María T

2016-01-01

In 2011, Chile experienced an increase in the number of cases of IMD caused by Neisseria meningitidis group W. This epidemiological scenario prompted authorities to implement prevention strategies. As part of these strategies, the Institute of Public Heath of Chile conducted a cross-sectional study to determine the prevalence of pharyngeal carriage of N. meningitidis in a representative sample of healthy children and adolescents aged 10-19 years. The identification of presumptive N. meningitidis strains was performed by testing carbohydrate utilization in the National Reference Laboratory at the ISP. Association of meningococcal carriage with risk factors was analyzed by calculating the Odds Ratio. Selected variables were included in a logistic model for risk analyses. The prevalence of carriage of N. meningitidis was 6.5% (CI: 5.7-7.3%). Older age (carriers: 14.2±0.29 vs. non-carriers: 13.8±0.08 years old; p=0.009), cohabitation with children (carriers: 0.9±0.13 vs. non-carriers: 0.7±0.03; p=0.028), number of smoking cohabitants (carriers: 0.55±0.13 vs. non-carriers: 0.44±0.03) and frequent attendance to crowded social venues (carriers: 49% vs. non-carriers: 37%; p=0.008) were determined to favor carriage. Statistical modeling showed that meningococcal carriage was associated with older age (OR: 1.077, p-value: 0.002) and cohabitation with children (OR: 1.182, p-value: 0.02). Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Building 909, oblique view to southeast, 135 mm lens. Building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Building 909, oblique view to southeast, 135 mm lens. Building 908 at extreme right for context. - Travis Air Force Base, Handling Crew Building, North of W Street, Armed Forces Special Weapons Project Q Area, Fairfield, Solano County, CA

Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease

PubMed Central

Smith, Harry; Rogers, Sharon L; Smith, Helen V; Gillis, David; Siskind, Victor; Smith, Judith A

2013-01-01

Aims To quantify a range of haematological indicators of viral infection (leucocyte apoptosis, cytopenia of normal lymphocytes, reactive lymphocyte increase, neutropenia) in patients with recent onset invasive meningococcal disease (IMD), with a view to test the association of viral infection with IMD and identify possible haematological risk factors for its development. Subjects and methods 88 patients with recent onset IMD, classified on clinical severity as fatal (n=14), septic shock survived (n=26) and no shock (n=48), and 50 healthy controls were studied. Blood film microscopy and leucocyte counts were used to quantify the virus-associated indicators. Cocci-containing neutrophils were also quantified. Results All viral parameters were significantly more frequent or higher in patients than controls, with leucocyte apoptosis found only in the patients. A significant gradient in accord with clinical severity was found for neutrophil and lymphocyte apoptosis, neutropenia and cocci-containing neutrophils. Crucially, apoptotic neutrophils did not contain cocci, and cocci-containing neutrophils were not apoptotic. Conclusions The correlation between magnitude of neutrophil apoptosis and severity of IMD suggests a cause–effect relationship. We propose that neutrophil apoptosis is more likely a facilitator rather than an effect of IMD for these reasons: (1) apoptotic neutrophils did not contain cocci and cocci-containing neutrophils were not apoptotic, (2) leucocyte apoptosis is a recognised viral effect and (3) Neisseria meningitidis is incapable of producing a Panton–Valentine type leucocidin. The lymphocyte apoptosis which accompanies neutrophil death may contribute to risk by impairing the generation of microbicidal antibody. Leucocyte apoptosis is a morphological expression of viral immunosuppression and, we suggest, is a likely contributor to a range of viral effects. PMID:23801496

Meningococcal Polysaccharide Vaccine Failure in a Patient with C7 Deficiency and a Decreased Anticapsular Antibody Response

DTIC Science & Technology

2012-05-01

Because the patient had a history of meningococcal meningitis at age 10, archived serum was obtained for further analysis. Complement component C7...us.arrny.mil Submitted: 11/21/11; Revised: 01/17/ 12; Accepted: 01129/12 httpJ/dx.doi.orgl10.4161/hv.19517 did when he had meningitis ." The...found that 15 23% of adults with meningococcal meningitis had an underlying complement deficiency.3 The most common and most recencly described

An Intercity Outbreak of Meningococcal Meningitis in Adults

PubMed Central

Oill, Phyllis A.; Chow, Anthony W.; Roberto, Ronald R.; Guze, Lucien B.

1978-01-01

An intercity outbreak of meningococcal meningitis occurred in five adults, with the acute onset of symptoms developing in two of the patients after they returned to Los Angeles from the San Francisco Bay area. The secondary attack rate was 36.4 percent in this entirely adult household. The authors review reports of secondary cases in civilian epidemics, as well as recommendations for chemoprophylaxis in household contacts. PMID:636407

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

PubMed Central

Satterfield, Benjamin A.; Cross, Robert W.; Fenton, Karla A.; Borisevich, Viktoriya; Agans, Krystle N.; Deer, Daniel J.; Graber, Jessica; Basler, Christopher F.; Mire, Chad E.

2016-01-01

ABSTRACT Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. IMPORTANCE Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced

42 CFR 480.135 - Disclosure necessary to perform review responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

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42 CFR 480.135 - Disclosure necessary to perform review responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

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Code of Federal Regulations, 2013 CFR

2013-10-01

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Reduction in Neisseria meningitidis infection in Italy after Meningococcal C conjugate vaccine introduction: A time trend analysis of 1994–2012 series

PubMed Central

de Waure, Chiara; Miglietta, Alessandro; Nedovic, Darko; Mereu, Giovanna; Ricciardi, Walter

2016-01-01

The incidence of invasive meningococcal disease (IMD) in Italy is among the lowest in Europe. Meningococcal C conjugate vaccine (MCC) was introduced in 2005 for 12 months old infants. The aim of this study was to describe the epidemiology of IMD in Italy from 1994 to 2012 and to evaluate the impact of MCC introduction. Data about Neisseria meningitidis (N. meningitidis) cases were drawn from the National Surveillance of Invasive Bacterial Diseases. The average incidence of IMD during 1994–2012 in Italy was 0.36 per 100,000 (95%CI 0.30; 0.40). N. meningitidis B was the most frequent serogroup and infants less than 12 months old were the most affected. Joinpoint analysis showed a statistically significant reduction in the incidence of N. meningitidis C related IMD after MCC introduction: the Annual Percentage Change declined from 21.8 (95%CI 15.1; 28.9) in 1994–2005 to −19.9 (95%CI −28.2; −10.7) afterwards. No changes were observed with respect to N. meningitidis B related IMD. Poisson regression showed a statistically significant reduction in the incidence of IMD both associated to N. meningitidis C (Incidence Rate Ratio 0.33; 95%CI 0.29; 0.37) and due to all serogroups (Incidence Rate Ratio 0.70; 95%CI 0.65; 0.75) in the post-vaccination period compared to the pre-vaccination one. On the other hand, the incidence of N. meningitidis B related IMD did not decrease. Our results suggest that MCC had an impact in decreasing the incidence of N. meningitidis C related IMD. However, data on typing are incomplete and efforts are needed to make them available for studying the need and the impact of other meningococcal vaccines. PMID:26308192

42 CFR 480.135 - Disclosure necessary to perform review responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

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42 CFR 480.135 - Disclosure necessary to perform review responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

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A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

PubMed

Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

2016-10-17

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

PubMed

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets.

PubMed

Satterfield, Benjamin A; Cross, Robert W; Fenton, Karla A; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Graber, Jessica; Basler, Christopher F; Geisbert, Thomas W; Mire, Chad E

2016-07-15

Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological

Response to the Critique of "New Meningococcal Vaccine Recommendations under Consideration"

ERIC Educational Resources Information Center

Turner, James C.

2005-01-01

The CDC recently published the ACIP recommendations regarding the use of meningococcal conjugate vaccine. The report includes detailed epidemiologic and cost analysis information. At the conclusion of lengthy discussions, the ACIP voted unanimously to approve the recommendation as written. In this article, the author provides his counterreaction…

College and University Compliance With a Required Meningococcal Vaccination Law

PubMed Central

Castel, Amanda D.; Reed, Greg; Davenport, Marsha G.; Harrison, Lee H.; Blythe, David

2015-01-01

Objective Maryland became the first state to pass a vaccination law requiring college and university students living on campus to obtain a meningococcal vaccination or to sign a waiver refusing vaccination because college students are at increased risk for disease. The authors sought to identify how Maryland colleges addressed the law and determine whether schools were in full compliance. Participants The authors surveyed 32 college/university administrators via a self-administered questionnaire. Methods The authors calculated vaccination and waiver rates and assessed compliance with the law overall and with specific law components. Results Among 28 participating schools, annual vaccination rates and waiver rates among students during 2000–2004 ranged from 66%–76% and 12%–17%, respectively. Two (7%) schools were compliant with all components of the law. Conclusions Mandatory vaccination laws do not ensure compliance at the college and university level. Mandatory reporting, increased education, and collaboration between colleges and universities and public health agencies are needed. PMID:17967757

The immunomodulating V and W proteins of Nipah virus determine disease course.

PubMed

Satterfield, Benjamin A; Cross, Robert W; Fenton, Karla A; Agans, Krystle N; Basler, Christopher F; Geisbert, Thomas W; Mire, Chad E

2015-06-24

The viral determinants that contribute to Nipah virus (NiV)-mediated disease are poorly understood compared with other paramyxoviruses. Here we use recombinant NiVs (rNiVs) to examine the contributions of the NiV V and W proteins to NiV pathogenesis in a ferret model. We show that a V-deficient rNiV is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. Remarkably, rNiV lacking W expression results in a delayed and altered disease course with decreased respiratory disease and increased terminal neurological disease associated with altered in vitro inflammatory cytokine production. This study confirms the V protein as the major determinant of pathogenesis, also being the first in vivo study to show that the W protein modulates the inflammatory host immune response in a manner that determines the disease course.

Delayed Generalized Necrotic Purpuric Rash in a C6-Deficient 12-Year-Old Girl Treated for Group W Meningococcal Disease.

PubMed

Gaschignard, Jean; Hassani, Nailati; El Sissy, Carine; Bonacorsi, Stéphane; Dauger, Stéphane; Chomton, Maryline; Taha, Muhamed-Kheir; Levy, Michael

2018-02-22

We report an unusual case of generalized necrotic purpuric rash that started 48 hours after the initiation of effective third-generation cephalosporin therapy to treat Neisseria meningitidis W infection in a 12-year-old girl. The course was favorable with no shock, and she recovered completely without sequelae. This infection revealed C6 deficiency in our patient.

Genotypic and phenotypic characterization of the O-linked protein glycosylation system reveals high glycan diversity in paired meningococcal carriage isolates.

PubMed

Børud, Bente; Bårnes, Guro K; Brynildsrud, Ola Brønstad; Fritzsønn, Elisabeth; Caugant, Dominique A

2018-03-19

Species within the genus Neisseria display significant glycan diversity associated with the O -linked protein glycosylation ( pgl ) systems due to phase variation, polymorphic genes and gene content. The aim of this study was to examine in detail the pgl genotype and glycosylation phenotype in meningococcal isolates and the changes occurring during short-term asymptomatic carriage. Paired meningococcal isolates derived from 50 asymptomatic meningococcal carriers, taken about two months apart, were analyzed with whole genome sequencing. The O -linked protein glycosylation genes were characterized in detail using the Genome Comparator tool at the PubMLST.org database. Immunoblotting with glycan specific antibodies were used to investigate the protein glycosylation phenotype. All major pgl locus polymorphisms identified in N. meningitidis to date were present in our isolate collection, with the variable presence of pglG-pglH, both in combination with either pglB or pglB2. We identified significant changes and diversity in the pgl genotype and/or glycan phenotype in 96% of the paired isolates. There was also a high degree of glycan microheterogeneity, in which different variants of glycan structures were found at a given glycoprotein. The main mechanism responsible for the observed differences was phase variable expression of the involved glycosyltransferases and the O-acetyltransferase. To our knowledge, this is the first characterization of the pgl genotype and glycosylation phenotype in a larger strain collection. This study thus provides important insight into glycan diversity in N. meningitidis and phase variability changes that influence the expressed glycoform repertoire during meningococcal carriage. Importance Bacterial meningitis is a serious global health problem and one of the major causative organisms is Neisseria meningitidis , which is also a common commensal in the upper respiratory tract of healthy humans. In bacteria, numerous loci involved in

Meningococcal vaccination in primary care amongst adolescents in North West England: an ecological study investigating associations with general practice characteristics.

PubMed

Blagden, Sarah; Hungerford, Daniel; Limmer, Mark

2018-01-27

In 2015 the meningococcal ACWY (MenACWY) vaccination was introduced amongst adolescents in England following increased incidence and mortality associated with meningococcal group W. MenACWY vaccination uptake data for 17-18 years old and students delivered in primary care were obtained for 20 National Health Service clinical commissioning groups (CCGs) via the ImmForm vaccination system. Data on general practice characteristics, encompassing demographics and patient satisfaction variables, were extracted from the National General Practice Profiles resource. Univariable analysis of the associations between practice characteristics and vaccination was performed, followed by multivariable negative binomial regression. Data were utilized from 587 general practices, accounting for ~8% of all general practices in England. MenACWY vaccination uptake varied from 20.8% to 46.8% across the CCGs evaluated. Upon multivariable regression, vaccination uptake increased with increasing percentage of patients from ethnic minorities, increasing percentage of patients aged 15-24 years, increasing percentage of patients that would recommend their practice and total Quality and Outcomes Framework achievement for the practice. Conversely, vaccination uptake decreased with increasing deprivation. This study has identified several factors independently associated with MenACWY vaccination in primary care. These findings will enable a targeted approach to improve general practice-level vaccination uptake. © The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

PubMed Central

Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

2016-01-01

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209

Routinely vaccinating adolescents against meningococcus: targeting transmission & disease.

PubMed

Vetter, Volker; Baxter, Roger; Denizer, Gülhan; Sáfadi, Marco A P; Silfverdal, Sven-Arne; Vyse, Andrew; Borrow, Ray

2016-05-01

Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable.

[Approximation to the dynamics of meningococcal meningitis through dynamic systems and time series].

PubMed

Canals, M

1996-02-01

Meningococcal meningitis is subjected to epidemiological surveillance due to its severity and the occasional presentation of epidemic outbreaks. This work analyses previous disease models, generate new ones and analyses monthly cases using ARIMA time series models. The results show that disease dynamics for closed populations is epidemic and the epidemic size is related to the proportion of carriers and the transmissiveness of the agent. In open populations, disease dynamics depends on the admission rate of susceptible and the relative admission of infected individuals. Our model considers a logistic populational growth and carrier admission proportional to populational size, generating an endemic dynamics. Considering a non-instantaneous system response, a greater realism is obtained establishing that the endemic situation may present a dynamics highly sensitive to initial conditions, depending on the transmissiveness and proportion of susceptible individuals in the population. Time series model showed an adequate predictive capacity in terms no longer than 10 months. The lack of long term predictability was attributed to local changes in the proportion of carriers or on transmissiveness that lead to chaotic dynamics over a seasonal pattern. Predictions for 1995 and 1996 were obtained.

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

PubMed Central

2015-01-01

Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.

PubMed

Cordeiro, Ana Paula; Silva Pereira, Rosiane Aparecida; Chapeaurouge, Alex; Coimbra, Clarice Semião; Perales, Jonas; Oliveira, Guilherme; Sanchez Candiani, Talitah Michel; Coimbra, Roney Santos

2015-01-01

Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis.

Routinely vaccinating adolescents against meningococcus: targeting transmission & disease

PubMed Central

Vetter, Volker; Baxter, Roger; Denizer, Gülhan; Sáfadi, Marco A. P.; Silfverdal, Sven-Arne; Vyse, Andrew; Borrow, Ray

2016-01-01

ABSTRACT Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable. PMID:26651380

W. W. "Mo" Cleland: a catalytic life.

PubMed

Dunaway-Mariano, Debra; Holden, Hazel M; Raushel, Frank M

2013-12-23

Professor W. Wallace Cleland, the architect of modern steady-state enzyme kinetics, died on March 6, 2013, from injuries sustained in a fall outside of his home. He will be most remembered for giving the enzyme community Ping-Pong kinetics and the invention of dithiothreitol (DTT). He pioneered the utilization of heavy atom isotope effects for the elucidation of the chemical mechanisms of enzyme-catalyzed reactions. His favorite research journal was Biochemistry, in which he published more than 135 papers beginning in 1964 with the disclosure of DTT.

Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

PubMed

Caugant, D A; Frøholm, L O; Bøvre, K; Holten, E; Frasch, C E; Mocca, L F; Zollinger, W D; Selander, R K

1986-07-01

Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

Neisseria meningitidis; clones, carriage, and disease.

PubMed

Read, R C

2014-05-01

Neisseria meningitidis, the cause of meningococcal disease, has been the subject of sophisticated molecular epidemiological investigation as a consequence of the significant public health threat posed by this organism. The use of multilocus sequence typing and whole genome sequencing classifies the organism into clonal complexes. Extensive phenotypic, genotypic and epidemiological information is available on the PubMLST website. The human nasopharynx is the sole ecological niche of this species, and carrier isolates show extensive genetic diversity as compared with hyperinvasive lineages. Horizontal gene exchange and recombinant events within the meningococcal genome during residence in the human nasopharynx result in antigenic diversity even within clonal complexes, so that individual clones may express, for example, more than one capsular polysaccharide (serogroup). Successful clones are capable of wide global dissemination, and may be associated with explosive epidemics of invasive disease. © 2014 The Author Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Use, location, and timeliness of clinical microbiology testing in Georgia for select infectious diseases.

PubMed

Brzozowski, Amanda K; Silk, Benjamin J; Berkelman, Ruth L; Loveys, Deborah A; Caliendo, Angela M

2012-01-01

Although clinical microbiology testing facilitates both public health surveillance of infectious diseases and patient care, research on testing patterns is scant. We surveyed hospital laboratories in Georgia to assess their diagnostic testing practices. Using e-mail, all directors of hospital laboratories in Georgia were invited to participate. The survey focused on timing and location of diagnostic testing in 2006 for 6 reportable diseases: giardiasis, legionellosis, meningococcal disease, pertussis, Rocky Mountain spotted fever, and West Nile virus disease. Of 141 laboratories, 62 (44%) responded to the survey. Hospitals varied widely in their use of diagnostic testing in 2006, with 95.1% testing for meningococcal disease, but only 66.1% and 63.3% testing for legionellosis and West Nile virus disease, respectively. Most laboratories (91%) performed gram stain/culture to diagnose meningococcal disease in-house and 23% performed ova and parasite panels for giardiasis were conducted in-house. Fewer than 11% of laboratories performed in-house testing for the remaining diseases. Laboratories affiliated with small hospitals (≤100 beds) were more likely to send specimens for outside testing compared with laboratories associated with large hospitals (>250 beds). Median turnaround time for ova and parasite panel testing for giardiasis was significantly shorter for in-house testing (1.0 days) than within-system (2.25 days) or outside laboratory (3.0 days) testing (P = .0003). No laboratories reported in-house testing for meningococcal disease, pertussis, or Rocky Mountain spotted fever using polymerase chain reaction. Many hospitals did not order diagnostic tests for important infectious diseases during 2006, even for relatively common diseases. In addition, hospital laboratories were unlikely to perform diagnostic testing in-house; sending specimens to an outside laboratory may result in substantial delays in receiving results. These unsettling findings have adverse

Modulation of the biological activities of meningococcal endotoxins by association with outer membrane proteins is not inevitably linked to toxicity.

PubMed Central

Quakyi, E K; Hochstein, H D; Tsai, C M

1997-01-01

Meningococcal sepsis results partly from overproduction of host cytokines after macrophages interact with endotoxin. To obtain less toxic and highly immunomodulatory meningococcal endotoxins for prophylactic purposes, we investigated the relationship between endotoxicity and immunomodulatory activity of several endotoxin preparations from Neisseria meningitidis group B. Using the D-galactosamine-sensitized mouse model to determine endotoxin lethality, we found that the toxicity of purified lipooligosaccharide (LOS) from M986, a group B disease strain, was three to four times higher than those of purified LOSs from the noncapsulated strains M986-NCV-1 and OP-, the truncated-LOS mutant. The LOSs of outer membrane vesicles (OMVs) and detergent-treated OMVs (D-OMVs) from the three strains were 2 to 3 and over 300 times less toxic than the purified LOSs, respectively. Intraperitoneal administration of these preparations induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum 2 h after injections. However, repeated doses of low- and high-toxicity preparations induced lower amounts of TNF-alpha and IL-6, i.e., LOS tolerance. Injection of mice with low doses of LOS was as effective as injection with high doses in inducing tolerance. Peritoneal macrophages from tolerant mice pretreated with either high- or low-toxicity LOS preparations produced only a fraction of the amounts of TNF-alpha and IL-6 produced by control groups in response to LOS ex vivo. Despite tolerance to LOS induced by pretreatment with reduced-toxicity preparations, killing of N. meningitidis M986 by macrophages from these animals was enhanced. Protection was achieved when mice treated with LOS, and especially that of D-OMVs, were challenged with live N. meningitidis. The least toxic LOS, that in D-OMVs, was most effective in inducing hyporesponsiveness to endotoxin in mice but protected them against challenge with N. meningitidis. No inevitable link between toxicity

Meningococcal carriage prevalence in university students, 1824 years of age in Santiago, Chile.

PubMed

Rodriguez, P; Alvarez, I; Torres, M T; Diaz, J; Bertoglia, M P; Carcamo, M; Seoane, M; Araya, P; Russo, M; Santolaya, M E

2014-09-29

Neisseria meningitidis invasive disease is a major public health problem. Pharyngeal carriage is considered a prerequisite for invasive infection. Prevalence reaches 10% in general population and up to 30% in the 20-24 years age group. The aim of this study was to asses pharyngeal carriage prevalence in healthy subjects aged 18-24 years, and as secondary endpoints evaluate known risk factors, to identify serogroups and sequence in the isolated strains. Cross-sectional study in 500 healthy subjects; students from Universidad de Chile aged 18-24 years, Santiago, Chile, October 2012. Each subject underwent a risk factor survey prior to throat culture sampling. Samples were processed in one central Microbiology Laboratory of Hospital Luis Calvo Mackenna and serogrouping and sequencing was performed at Instituto de Salud Pública de Chile. We obtained throat samples from 500 healthy subjects, 20 (4%) positive for N. meningitidis. Of positive strains 20% were serogroup B, 15% W and the rest non groupable. The median age was 20 years, 50% were men. Of the risk factors evaluated, 24% were current smokers, 16% shared a room, 72% had kissed someone during the last month, 64% had gone to pub and 76% had consumed alcohol in the same period of time. Literatures meningococcal carriage prevalence reaches up to 30% in people aged 18-24 years. Prevalence in our study was 4%. Different interpretations could be given; one could be the absence of overcrowding in our students because of the lack of dorms in our scholar system and also the characteristics of our enrolled group. Our results suggest the necessity to extend the study to other age groups and to other cities, to better understand the Chilean reality, as well as others regions of America, considering that these results cannot be extrapolated to another countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ex vivo model of meningococcal bacteremia using human blood for measuring vaccine-induced serum passive protective activity.

PubMed

Plested, Joyce S; Welsch, Jo Anne; Granoff, Dan M

2009-06-01

The binding of complement factor H (fH) to meningococci was recently found to be specific for human fH. Therefore, passive protective antibody activity measured in animal models of meningococcal bacteremia may overestimate protection in humans, since in the absence of bound fH, complement activation is not downregulated. We developed an ex vivo model of meningococcal bacteremia using nonimmune human blood to measure the passive protective activity of stored sera from 36 adults who had been immunized with an investigational meningococcal multicomponent recombinant protein vaccine. Before immunization, human complement-mediated serum bactericidal activity (SBA) titers of > or = 1:4 against group B strains H44/76, NZ98/254, and S3032 were present in 19, 11, and 8% of subjects, respectively; these proportions increased to 97, 22, and 36%, respectively, 1 month after dose 3 (P < 0.01 for H44/76 and S3032). Against the two SBA-resistant strains, NZ98/254 and S3032, passive protective titers of > or = 1:4 were present in 11 and 42% of sera before immunization, respectively, and these proportions increased to 61 and 94% after immunization (P < 0.001 for each strain). Most of the sera with SBA titers of <1:4 and passive protective activity showed a level of killing in the whole-blood assay (>1 to 2 log(10) decreases in CFU/ml during a 90-min incubation) similar to that of sera with SBA titers of > or = 1:4. In conclusion, passive protective activity was 2.6- to 2.8-fold more frequent than SBA after immunization. The ability of SBA-negative sera to kill Neisseria meningitidis in human blood where fH is bound to the bacteria provides further evidence that SBA titers of > or = 1:4 measured with human complement may underestimate meningococcal immunity.

An Investigation Into Criteria Commonly Used by the FAA to Grant Relief to Part 135 Operators Under FAR Sections: 135.213, 135.219, and/or 135.225

NASA Technical Reports Server (NTRS)

Williams, Louis J.; Heck, Michael L.; Burgess, Malcolm A.; Stough, H. P. (Technical Monitor)

2002-01-01

The objective of this study was to determine the criteria commonly used by the FAA to grant waivers, exemptions, or deviations to FAR Part 135, Sections 135.213, 135.219, and 135.225 and the potential impact on Flight Information Services Data Link (FISDL) implementation. These aviation regulations address the requirements for the use of weather reports or forecasts when conducting operations under FAR Part 135. In this study a literature search was conducted to obtain historical records of requests for relief from the 3 FAR sections under consideration. The exemption request records were then analyzed in order to determine the reasons given by the FAA for either granting or denying the request. In addition, FAA personnel and Part 135 operators were interviewed to determine the procedures used for satisfying the requirements of the 3 FAR sections.

Complement C5a Receptor 1 Exacerbates the Pathophysiology of N. meningitidis Sepsis and Is a Potential Target for Disease Treatment

PubMed Central

Herrmann, Johannes B.; Muenstermann, Marcel; Strobel, Lea; Schubert-Unkmeir, Alexandra; Woodruff, Trent M.; Klos, Andreas

2018-01-01

ABSTRACT Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention is often sought too late, i.e., when the systemic inflammatory response is already unleashed. This in turn limits the success of antibiotic treatment. The complement system is generally accepted as the most important innate immune determinant against invasive meningococcal disease since it protects the host through the bactericidal membrane attack complex. However, complement activation concomitantly liberates the C5a peptide, and it remains unclear whether this potent anaphylatoxin contributes to protection and/or drives the rapidly progressing immunopathogenesis associated with meningococcal disease. Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100-fold, respectively, consistent with the contribution of these components to protection. In clear contrast, C5ar1−/− mice resisted invasive meningococcal infection and cleared N. meningitidis more rapidly than wild-type (WT) animals. This favorable outcome stemmed from an ameliorated inflammatory cytokine response to N. meningitidis in C5ar1−/− mice in both in vivo and ex vivo whole-blood infections. In addition, inhibition of C5aR1 signaling without interference with the complement bactericidal activity reduced the inflammatory response also in human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse survival and lowered meningococcal burden even when the treatment was administered after sepsis induction. Together, our findings demonstrate that C5aR1 drives the pathophysiology associated with meningococcal sepsis and provides a promising target for adjunctive therapy. PMID:29362231

Measurements of the Fuel Mileage of a KC-135 Aircraft with and Without Winglets

NASA Technical Reports Server (NTRS)

Temanson, G. E.

1982-01-01

The KC-135A Winglet Flight Research and Demonstration Program was a joint effort of the Air Force, NASA and the Boeing Military Airplane Company to flight test winglets on the KC-135A. The primary objective of the program was to verify the cruise performance improvements predicted by analysis and wind tunnel tests. Flight test data were obtained for winglets positioned at 15 deg cant/-2 deg incidence, 0 deg cant/-4 deg incidence, 15 deg cant/-4 deg incidence and for winglets off (baseline). Both fuel mileage and drag measurements were obtained. The 15 deg cant/-4 deg incidence winglet configuration provided the greatest performance improvement. The flight test measured fuel mileage improvement for a 0.78 Mach number was 3.1 percent at 8 x 10(5) pounds W/delta and 5.5 percent at 1.05 x 10(6) pounds W/delta. Correcting the flight measured data for surface pressure differences between wind tunnel and flight resulted in a fuel mileage improvement of 4.4 percent at 8 x 10(5) pounds W/delta and 7.2 percent at 1.05 x 10(6) pounds W/delta. The agreement between the fuel mileage and drag data was excellent.

Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.

PubMed

Snape, Matthew D; Maclennan, Jenny M; Lockhart, Stephen; English, Mike; Yu, Ly-Mee; Moxon, Richard E; Pollard, Andrew J

2009-02-01

Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

T135I substitution in the nonstructural protein 2C enhances foot-and-mouth disease virus replication.

PubMed

Yuan, Tiangang; Wang, Haiwei; Li, Chen; Yang, Decheng; Zhou, Guohui; Yu, Li

2017-12-01

The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19-20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143. The rescued virus O/YS/CHA/05-Δ3A exhibited slower growth kinetics and formed smaller plaques compared to O/YS/CHA/05 in both BHK-21 and IBRS-2 cells, indicating that the 60-amino acid deletion in the 3A protein impaired FMDV replication. After 14 passages in BHK-21 cells, the replication capacity of the passaged virus O/YS/CHA/05-Δ3A-P14 returned to a level similar to the wild-type virus, suggesting that amino acid substitutions responsible for the enhanced replication capacity occurred in the genome of O/YS/CHA/05-Δ3A-P14. By sequence analysis, two amino acid substitutions, P153L in VP1 and T135I in 2C, were found in the O/YS/CHA/05-Δ3A-P14 genome compared to the O/YS/CHA/05-Δ3A genome. Subsequently, the amino acid substitutions VP1 P153L and 2C T135I were separately introduced into O/YS/CHA/05-Δ3A to rescue mutant viruses for examining their growth kinetics. Results showed that the 2C T135I instead of the VP1 P153L enhanced the virus replication capacity. The 2C T135I substitution also improved the replication of the wild-type virus, indicating that the effect of 2C T135I substitution on FMDV replication is not associated with the 3A deletion. Furthermore, our results showed that the T135I substitution in the nonstructural protein 2C enhanced O/YS/CHA/05 replication through promoting viral RNA synthesis.

Impact of meningococcal C conjugate vaccination four years after introduction of routine childhood immunization in Brazil.

PubMed

Andrade, Ana Lucia; Minamisava, Ruth; Tomich, Lisia Moura; Lemos, Ana Paula; Gorla, Maria Cecilia; de Cunto Brandileone, Maria Cristina; Domingues, Carla Madga S; de Moraes, Camile; Policena, Gabriela; Bierrenbach, Ana Luiza

2017-04-11

Routine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12-15months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program. We performed an ecological quasi-experimental design from 2008 to 2014 using a deterministic linkage between the National Notification and the National Reference Laboratory databases for meningitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post-vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of São Paulo. A total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged <12months and no second incident peak was observed for adolescents. For Brazil, MenC rates were reduced by 67.2% (95%CI 43.0-91.4%) for infants <12months of age, 92.0% (77.3-106.8%) for the age-group 12-23months, and 64.6% (24.6-104.5%) for children aged 2-4years. For children 5-9years old, MenC rates reduced 19.2% (9.5-28.9%). Overall, 955 MenC cases were averted in Brazil in individuals aged <40years after MCC vaccination. Results from São Paulo State, mirror the patterns seen in Brazil. After four years of infants and toddlers vaccination start, MenC invasive disease reduced in the target population. This investigation provide a robust baseline to ascertain how much the upcoming catch-up dose in 12-13years of age will accelerate the decrease in MenC incidence rates among youths in Brazil. Copyright © 2017

Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants.

PubMed

Collins, Clare L; Ruggeberg, Jens U; Balfour, Gail; Tighe, Helen; Archer, Marion; Bowen-Morris, Jane; Diggle, Linda; Borrow, Ray; Balmer, Paul; Buttery, Jim P; Moxon, E Richard; Pollard, Andrew J; Heath, Paul T

2005-11-01

Protein-polysaccharide conjugate vaccines against Neisseria meningitidis serogroup C were introduced into the U.K. routine immunization schedule in 1999. This study is the first to describe both persistence of antibody and evidence for induction of immune memory using meningococcal C conjugate (MCC) vaccine in preterm infants. Immunogenicity and induction of immunologic memory by as MCC vaccine was assessed in premature infants; 62 preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4 months of age). A meningococcal C polysaccharide challenge was administered at 12 months of age. Both groups achieved similar protective titers after primary immunization that then waned significantly by 1 year of age. Postchallenge serum bactericidal activity was significantly lower in preterm infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold rise in serum bactericidal activity (P = 0.07). MCC vaccine is immunogenic and primes for immunologic memory in preterm infants. The decreased memory responses in these preterm infants in conjunction with waning clinical efficacy data for all U.K. infants suggest a role for a routine booster dose of vaccine in all infants receiving MCC, especially those born preterm.

Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

PubMed Central

Lynn, Freyja; Mocca, Brian; Borrow, Ray; Findlow, Helen; Hassan-King, Musa; Preziosi, Marie-Pierre; Idoko, Olubukola; Sow, Samba; Kulkarni, Prasad; LaForce, F. Marc

2014-01-01

A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC′) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC′ and then used the SBA assay with hC′ (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC′ lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC′. hSBA titers determined using three independent lots of pooled hC′ were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC′ is feasible and showed that PsA-TT was highly immunogenic in African toddlers. PMID:24671551

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

PubMed

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

2007-01-01

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

Medical Surveillance Monthly Report (MSMR). Volume 13, Number 2, February/March 2007

DTIC Science & Technology

2007-03-01

13/No. 2 1 10 100 1,000 10,000 100,000 Influenza Varicella Hep B Pertussis Hep A Mumps Meningococcal disease Vaccine-preventable disease R ep or te... pertussis (ICD- 9: 033), mumps (ICD-9: 072), influenza (ICD-9: 487), hepatitis B (ICD-9: 070.2, 070.3), and hepatitis A (ICD- 9: 070.0, 070.1) were defined by...Influenza Varicella Hep B w/o coma Pertussis Hep A w/o coma MSMR 17Vol. 13/No. 2 conditions should account for potential changes in case ascertainment and

Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015

PubMed Central

Smith-Palmer, Alison; Oates, Ken; Webster, Diana; Taylor, Sarah; Scott, Kevin J; Smith, Gemma; Parcell, Benjamin; Lindstrand, Ann; Wallensten, Anders; Fredlund, Hans; Widerström, Micael; McMenamin, Jim

2016-01-01

The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner. PMID:27918267

The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease.

PubMed

Luo, Yin; Friese, Olga V; Runnels, Herbert A; Khandke, Lakshmi; Zlotnick, Gary; Aulabaugh, Ann; Gore, Thomas; Vidunas, Eugene; Raso, Stephen W; Novikova, Elena; Byrne, Emilia; Schlittler, Michael; Stano, Donald; Dufield, Robert L; Kumar, Sandeep; Anderson, Annaliesa S; Jansen, Kathrin U; Rouse, Jason C

2016-11-01

Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture.

Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

PubMed

Sakaida, Isao; Tsuchiya, Masako; Kawaguchi, Kotarou; Kimura, Teruaki; Terai, Shuji; Okita, Kiwamu

2003-06-01

The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis. The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined. TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner. These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.

Safety of a Meningococcal Group B Vaccine Used in Response to Two University Outbreaks

ERIC Educational Resources Information Center

Duffy, Jonathan; Johnsen, Peter; Ferris, Mary; Miller, Mary; Leighton, Kevin; McGilvray, Mark; McNamara, Lucy; Breakwell, Lucy; Yu, Yon; Bhavsar, Tina; Briere, Elizabeth; Patel, Manisha

2017-01-01

Objective: To assess the safety of meningococcal group B (MenB)-4C vaccine. Participants: Undergraduates, dormitory residents, and persons with high-risk medical conditions received the MenB-4C vaccine two-dose series during mass vaccination clinics from 12/2013 through 11/2014. Methods: Adverse events (AEs) were identified by 15 minutes of…

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

Integrated Risk Information System (IRIS)

Hexahydro - 1,3,5 - trinitro - 1,3,5 - triazine ( RDX ) ; CASRN 121 - 82 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health

Acceptability of meningococcal serogroup B vaccine among parents and health care workers in Italy: A survey

PubMed Central

Mameli, Chiara; Faccini, Marino; Mazzali, Cristina; Picca, Marina; Colella, Giacomo; Duca, Pier Giorgio; Zuccotti, Gian Vincenzo

2014-01-01

A new meningococcal serogroup B vaccine (4CMenB) has recently been licensed. This study assessed the acceptability of 4CMenB vaccine among parents and healthcare workers (HCWs). From May to July 2013 in Milan, Italy, self-administered questionnaires were distributed to 2050 parents of infants presenting at immunization clinics for the mandatory hexavalent vaccination and submitted to 350 HCWs involved in immunization practices. 1842 parents (89.1%) responded to the survey; 64.4% of parents wanted their child to receive the 4CMenB vaccine and 5.1% would not vaccinate their children. Multivariate analysis showed that recognition of the severity of meningitis [a life threatening vs a mild or unthreatening disease (Odds ratio (OR): 2.3; confidence interval (CI): 1.4–3.6], awareness of vaccination as a beneficial preventive measure (very beneficial vs not beneficial OR = 6.4; CI 3.0–13.7) and knowledge of the Meningococcal C vaccine (OR = 1.4; CI 1.1–1.8) were strongly associated to willingness to receive 4CMenB vaccine. On the contrary, level of education was associated with refusal of immunization (university vs education level lower than middle school OR = 0.68; CI 0.47–0.97). Among the parents who were willing to immunize their children, 66.9% would agree with three injections to be administered during the same visit. A total of 291 HCWs (83.1%) agreed to participate in the survey; 73% considered 4CMenB vaccine a priority in infants’ immunization schedule; 26.8% of HCWs suggested the concomitant administration with routine infant immunization. Parental and HCWs acceptability of 4CMenB vaccine was high. Increasing knowledge about meningitis and vaccine prevention might further increase the acceptability of this vaccine. PMID:25483638

Evolution of Sequence Type 4821 Clonal Complex Meningococcal Strains in China from Prequinolone to Quinolone Era, 1972–2013

PubMed Central

Guo, Qinglan; Mustapha, Mustapha M.; Chen, Mingliang; Qu, Di; Zhang, Xi; Harrison, Lee H.

2018-01-01

The expansion of hypervirulent sequence type 4821 clonal complex (CC4821) lineage Neisseria meningitidis bacteria has led to a shift in meningococcal disease epidemiology in China, from serogroup A (MenA) to MenC. Knowledge of the evolution and genetic origin of the emergent MenC strains is limited. In this study, we subjected 76 CC4821 isolates collected across China during 1972–1977 and 2005–2013 to phylogenetic analysis, traditional genotyping, or both. We show that successive recombination events within genes encoding surface antigens and acquisition of quinolone resistance mutations possibly played a role in the emergence of CC4821 as an epidemic clone in China. MenC and MenB CC4821 strains have spread across China and have been detected in several countries in different continents. Capsular switches involving serogroups B and C occurred among epidemic strains, raising concerns regarding possible increases in MenB disease, given that vaccines in use in China do not protect against MenB. PMID:29553310

Paediatric meningococcaemia in northwestern Ontario, Canada: a case for publicly funded meningococcal B vaccination

PubMed Central

Tsang, Raymond S. W.; Ulanova, Marina

2016-01-01

Introduction: Neisseria meningitidis serogroup B is an important infectious agent in developed countries, including Canada. Infants are particularly susceptible to infection with serogroup B because of immature immune systems, pathogen virulence factors and changing serogroup dynamics in the post-vaccination era. Currently, the Ontario provincial government does not include serogroup B in its routine publicly funded meningococcal vaccination program. Case Presentation: A formerly well 14-month-old male presented to a tertiary hospital emergency department with fever, minor respiratory problems, diffuse purpuric rash, distended abdomen, tachycardia, and history of one episode of vomiting and melena each. Meningococcaemia was immediately suspected, and he was treated with ceftriaxone, cefotaxime and vancomycin before transfer to a different acute care facility within 12 h. N. meningitidis serogroup B, sensitive to ceftriaxone and penicillin, was identified in his blood. The patient developed gangrene of the lower legs and underwent bilateral below-knee amputation 8 days post-admission. Conclusion: This instance of meningococcaemia with extensive sequelae is an example of the various serious outcomes of meningococcal infection. It provides persuasive reason for routine publicly funded vaccination against N. meningitidis serogroup B in Ontario. PMID:28348748

STS_135_Landing

NASA Image and Video Library

2011-07-21

NASA astronaut Chris Ferguson, STS-135 commander, examines the thermal tiles of the orbiter after the space shuttle Atlantis landed at the Kennedy Space Center in Florida completing STS-135, the final mission of the NASA shuttle program, on Thursday, July 21, 2011. ( NASA Photo / Houston Chronicle, Smiley N. Pool )

Acquisition and carriage of meningococci in marine commando recruits.

PubMed Central

Riordan, T.; Cartwright, K.; Andrews, N.; Stuart, J.; Burris, A.; Fox, A.; Borrow, R.; Douglas-Riley, T.; Gabb, J.; Miller, A.

1998-01-01

Meningococcal acquisition is a prerequisite for invasive disease. Three hundred and eleven male marine commando recruits were studied throughout 29 weeks of basic training to identify factors influencing meningococcal carriage and acquisition including troop number, season, smoking, respiratory infection, antibiotic usage and nasopharyngeal bacterial interference flora. A high carriage rate on entry to training (118/311, 37.9%) and subsequent sustained high rates of meningococcal acquisition were found. Of the potential factors examined, only active and passive smoking were found to be associated significantly with meningococcal carriage on entry. The association between active smoking and meningococcal carriage was dose-dependent, with odds ratios (OR) of 2.2 (95% CIs 1.0-4.8) and 7.2 (95% CIs 2.3-22.9) for light and heavy smokers respectively. Passive smoking predisposed independently to carriage (OR 1.8, 95% CIs 1.1-3.0). Active and passive smoking combined to give an attributable risk for meningococcal carriage of 33%. In contrast, despite a high and sustained rate of meningococcal acquisition in the study population, none of the risk factors investigated, including active smoking, was associated significantly with meningococcal acquisition. No cases of meningococcal disease occurred during the 16-month study period. Therefore smoking may increase the duration of meningococcal carriage rather than the rate of acquisition, consistent with the increased risk of meningococcal disease from passive as opposed to active smoking. Public health measures that reduce the prevalence of smoking should reduce the risk of meningococcal disease. PMID:10030697

[Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997].

PubMed

da Silva, Alfred; Parent du Châtelet, Isabelle; Beckr Gaye, Abou; Dompnier, Jean-Pierre; Seck, Ibrahima

2003-01-01

Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the

14 CFR 135.201 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Applicability. 135.201 Section 135.201 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... Limitations and Weather Requirements § 135.201 Applicability. This subpart prescribes the operating...

14 CFR 135.201 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Applicability. 135.201 Section 135.201 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... Limitations and Weather Requirements § 135.201 Applicability. This subpart prescribes the operating...

14 CFR 135.201 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Applicability. 135.201 Section 135.201 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... Limitations and Weather Requirements § 135.201 Applicability. This subpart prescribes the operating...

14 CFR 135.201 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Applicability. 135.201 Section 135.201 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... Limitations and Weather Requirements § 135.201 Applicability. This subpart prescribes the operating...

14 CFR 135.201 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Applicability. 135.201 Section 135.201 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... Limitations and Weather Requirements § 135.201 Applicability. This subpart prescribes the operating...

14 CFR 121.135 - Contents.

Code of Federal Regulations, 2010 CFR

2001-01-01

... 14 Aeronautics and Space 2 2001-01-01 2001-01-01 false Contents. 121.135 Section 121.135 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (Continued) AIR CARRIERS..., FLAG, AND SUPPLEMENTAL OPERATIONS Manual Requirements § 121.135 Contents. (a) Each manual required by...

28 CFR 115.135 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false [Reserved] 115.135 Section 115.135 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Training and Education § 115.135 [Reserved] Screening for Risk of Sexual Victimization...

28 CFR 115.135 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false [Reserved] 115.135 Section 115.135 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Training and Education § 115.135 [Reserved] Screening for Risk of Sexual Victimization...

28 CFR 115.135 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false [Reserved] 115.135 Section 115.135 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Training and Education § 115.135 [Reserved] Screening for Risk of Sexual Victimization...

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

PubMed

Velentgas, Priscilla; Amato, Anthony A; Bohn, Rhonda L; Chan, K Arnold; Cochrane, Thomas; Funch, Donnie P; Dashevsky, Inna; Duddy, April L; Gladowski, Patricia; Greenberg, Steven A; Kramer, Judith M; McMahill-Walraven, Cheryl; Nakasato, Cynthia; Spettell, Claire M; Syat, Beth L; Wahl, Peter M; Walker, Alexander M; Zhang, Fang; Brown, Jeffrey S; Platt, Richard

2012-12-01

A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk. Copyright © 2012 John Wiley & Sons, Ltd.

STS_135_CEIT

NASA Image and Video Library

2011-04-07

JSC2011-E-040358 (7 April 2011) --- NASA astronaut Doug Hurley, STS-135 pilot, exits the hatch of the space shuttle Atlantis during the STS-135 Crew Equipment Interface Test (CEIT) in the Orbiter Processing Facility at NASA?s Kennedy Space Center, Florida on April 7, 2011. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

33 CFR 135.101 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Purpose. 135.101 Section 135.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Levy of Fees § 135.101...

33 CFR 135.101 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Purpose. 135.101 Section 135.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Levy of Fees § 135.101...

33 CFR 135.101 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Purpose. 135.101 Section 135.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Levy of Fees § 135.101...

33 CFR 135.101 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Purpose. 135.101 Section 135.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Levy of Fees § 135.101...

33 CFR 135.101 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Purpose. 135.101 Section 135.101 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Levy of Fees § 135.101...

Project həli?dx(w)/Healthy Hearts Across Generations: development and evaluation design of a tribally based cardiovascular disease prevention intervention for American Indian families.

PubMed

Walters, Karina L; LaMarr, June; Levy, Rona L; Pearson, Cynthia; Maresca, Teresa; Mohammed, Selina A; Simoni, Jane M; Evans-Campbell, Teresa; Fredriksen-Goldsen, Karen; Fryberg, Sheryl; Jobe, Jared B

2012-08-01

American Indian and Alaska Native (AIAN) populations are disproportionately at risk for cardiovascular disease (CVD), diabetes, and obesity, compared with the general US population. This article describes the həli?dx(w)/Healthy Hearts Across Generations project, an AIAN-run, tribally based randomized controlled trial (January 2010-June 2012) designed to evaluate a culturally appropriate CVD risk prevention program for AI parents residing in the Pacific Northwest of the United States. At-risk AIAN adults (n = 135) were randomly assigned to either a CVD prevention intervention arm or a comparison arm focusing on increasing family cohesiveness, communication, and connectedness. Both year-long conditions included 1 month of motivational interviewing counseling followed by personal coach contacts and family life-skills classes. Blood chemistry, blood pressure, body mass index, food intake, and physical activity were measured at baseline and at 4- and 12-month follow-up times.

5 CFR 838.135 - Settlements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Settlements. 838.135 Section 838.135 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) COURT... § 838.135 Settlements. (a) OPM must comply with the terms of a properly filed court order acceptable for...

22 CFR 135.30 - Changes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Changes. 135.30 Section 135.30 Foreign... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 135.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

Developmental analysis and influence of genetic background on the Lhx3 W227ter mouse model of combined pituitary hormone deficiency disease.

PubMed

Prince, Kelly L; Colvin, Stephanie C; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A; Rhodes, Simon J

2013-02-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3(W227ter/W227ter) mouse model. Lhx3(W227ter/W227ter) embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3(W227ter/W227ter) genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3(W227ter/W227ter) animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3(W227ter/W227ter) mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3(W227ter/W227ter) mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases.

Developmental Analysis and Influence of Genetic Background on the Lhx3 W227ter Mouse Model of Combined Pituitary Hormone Deficiency Disease

PubMed Central

Prince, Kelly L.; Colvin, Stephanie C.; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A.

2013-01-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3W227ter/W227ter mouse model. Lhx3W227ter/W227ter embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3W227ter/W227ter genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3W227ter/W227ter animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3W227ter/W227ter mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3W227ter/W227ter mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases. PMID:23288907

21 CFR 135.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Definitions. 135.3 Section 135.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FROZEN DESSERTS General Provisions § 135.3 Definitions. For the purposes of this part, a...

STS-135_VMS

NASA Image and Video Library

2011-03-02

JSC2011-E-040204 (2 March 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, prepares for departure from Moffett Field in a T-38 trainer home to Houston after the crew of STS-135 trained in the Vertical Motion Simulator (VMS) at NASA's Ames Research Center in Mountain View, Calif. on March 2, 2011, Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_CEIT

NASA Image and Video Library

2011-04-08

JSC2011-E-040366 (8 April 2011) --- Close-up photo of tools taken during the STS-135 crew members' inspection of the equipment they will use in space. The inspection was part of the STS-135 Crew Equipment Interface Test (CEIT) conducted April 8, 2011 at NASA?s Kennedy Space Center in Florida. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

Communication Challenges During the Development and Introduction of a New Meningococcal Vaccine in Africa.

PubMed

Berlier, Monique; Barry, Rodrigue; Shadid, John; Sirica, Coimbra; Brunier, Alison; Hasan, Hayatee; Bouma, Enricke

2015-11-15

A new group A meningococcal conjugate vaccine was developed to eliminate deadly meningitis epidemics in sub-Saharan Africa. From the outset of the project, advocacy and communication strategies were developed and adjusted as the project evolved in Europe, Africa, India, and the United States. Communications efforts were evidence-based, and involved partnerships with the media and various stakeholders including African ministries of health, the World Health Organization, UNICEF, Gavi, the Centers for Disease Control and Prevention, and Médecins Sans Frontières. The implementation of an integrated communication strategy ensured the active cooperation of stakeholders while providing an organized and defined format for the dissemination of project-related developmental activities and the successful introduction of the vaccine. Early in the project, a communications strategy that engaged stakeholders and potential supporters was developed. The strategy was implemented and adapted as the project matured. Linked communication proved to be key to the successful wide-scale introduction of the PsA-TT (MenAfriVac) vaccine in Africa. © 2015 World Health Organization; licensee Oxford Journals.

Communication Challenges During the Development and Introduction of a New Meningococcal Vaccine in Africa

PubMed Central

Berlier, Monique; Barry, Rodrigue; Shadid, John; Sirica, Coimbra; Brunier, Alison; Hasan, Hayatee; Bouma, Enricke

2015-01-01

Background. A new group A meningococcal conjugate vaccine was developed to eliminate deadly meningitis epidemics in sub-Saharan Africa. Methods. From the outset of the project, advocacy and communication strategies were developed and adjusted as the project evolved in Europe, Africa, India, and the United States. Communications efforts were evidence-based, and involved partnerships with the media and various stakeholders including African ministries of health, the World Health Organization, UNICEF, Gavi, the Centers for Disease Control and Prevention, and Médecins Sans Frontières. Results. The implementation of an integrated communication strategy ensured the active cooperation of stakeholders while providing an organized and defined format for the dissemination of project-related developmental activities and the successful introduction of the vaccine. Conclusions. Early in the project, a communications strategy that engaged stakeholders and potential supporters was developed. The strategy was implemented and adapted as the project matured. Linked communication proved to be key to the successful wide-scale introduction of the PsA-TT (MenAfriVac) vaccine in Africa. PMID:26553674

40 CFR 135.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Purpose. 135.1 Section 135.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PRIOR NOTICE OF CITIZEN SUITS Prior Notice Under the Clean Water Act § 135.1 Purpose. (a) Section 505(a)(1) of the Clean Water...

40 CFR 135.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Purpose. 135.1 Section 135.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PRIOR NOTICE OF CITIZEN SUITS Prior Notice Under the Clean Water Act § 135.1 Purpose. (a) Section 505(a)(1) of the Clean Water...

40 CFR 135.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Purpose. 135.1 Section 135.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PRIOR NOTICE OF CITIZEN SUITS Prior Notice Under the Clean Water Act § 135.1 Purpose. (a) Section 505(a)(1) of the Clean Water...

40 CFR 135.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Purpose. 135.1 Section 135.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS PRIOR NOTICE OF CITIZEN SUITS Prior Notice Under the Clean Water Act § 135.1 Purpose. (a) Section 505(a)(1) of the Clean Water...

49 CFR 213.135 - Switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Switches. 213.135 Section 213.135 Transportation... TRANSPORTATION TRACK SAFETY STANDARDS Track Structure § 213.135 Switches. (a) Each stock rail must be securely seated in switch plates, but care shall be used to avoid canting the rail by overtightening the rail...

49 CFR 213.135 - Switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Switches. 213.135 Section 213.135 Transportation... TRANSPORTATION TRACK SAFETY STANDARDS Track Structure § 213.135 Switches. (a) Each stock rail must be securely seated in switch plates, but care shall be used to avoid canting the rail by overtightening the rail...

49 CFR 213.135 - Switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Switches. 213.135 Section 213.135 Transportation... TRANSPORTATION TRACK SAFETY STANDARDS Track Structure § 213.135 Switches. (a) Each stock rail must be securely seated in switch plates, but care shall be used to avoid canting the rail by overtightening the rail...

STS_135_STA

NASA Image and Video Library

2011-05-31

JSC2011-E-059480 (31 May 2011) --- NASA astronaut Sandy Magnus, STS-135 mission specialist, is seen on May 31 in the rear station of a T-38 which had been piloted by astronaut Doug Hurley, STS-135 pilot, and is now sitting just off the runway following arrival at NASA?s Kennedy Space Center in Florida. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_NBL

NASA Image and Video Library

2011-03-10

JSC2011-E-040220 (10 March 2011) --- NASA astronaut Rex Walheim (left), STS-135 mission specialist, and astronaut Mike Fossum are aided by divers as they work in a mock-up of the space shuttle's payload bay as the crew of STS-135 trains for a spacewalk in the Neutral Buoyancy Laboratory near NASA?s Johnson Space Center on March 10, 2011. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_NBL

NASA Image and Video Library

2011-03-10

JSC2011-E-040218 (10 March 2011) --- NASA astronaut Rex Walheim, STS-135 mission specialist, is aided by divers as he works with astronaut Mike Fossum in a mock-up of the space shuttle's payload bay as the crew of STS-135 trains for a spacewalk in the Neutral Buoyancy Laboratory near NASA?s Johnson Space Center on March 10, 2011. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

PubMed

Arru, G; Mameli, G; Deiana, G A; Rassu, A L; Piredda, R; Sechi, E; Caggiu, E; Bo, M; Nako, E; Urso, D; Mariotto, S; Ferrari, S; Zanusso, G; Monaco, S; Sechi, G; Sechi, L A

2018-03-31

Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su 19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su 19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su 19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS. © 2018 EAN.

BACTERIAL MENINGITIS AND OTHER DISEASES AFFECTING THE MENINGES—A Review of 349 Cases

PubMed Central

Cover, William L.

1949-01-01

Three hundred and forty-nine cases of disease affecting the meninges were observed at the San Bernardino County Charity Hospital in an eight year period. A total of 29 patients with meningococcal, H. influenzae and pneumococcal meningitis were treated. There were four deaths, of which three occurred during the first 24 hours in the hospital. Of 22 cases of unclassified meningitis, four probably were tuberculous, four probably were meningococcal and two probably were of virus origin. Under present treatment programs the differentiation between viral and bacterial meningitides is difficult and it is possible, therefore, that the reported incidence of the two groups may not represent the facts. Of 22 cases of unclassified meningitis, 12 had no specific characteristics which would permit a clinical diagnosis. One of the patients died. Of 70 cases of clinical meningitis, the infecting organism was identified in 69 per cent. Meningococcal meningitis made up only 17 per cent of 70 cases of purulent meningitis observed between July 1, 1945, and July 1, 1948. PMID:18137216

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis.

PubMed

Patel, M; Lee, C K

2001-01-01

Controlled trials over two decades ago showed that the polysaccharide vaccine prevented serogroup A meningococcal meningitis. Subsequent non-experimental studies suggested age-specific variations in the duration of protection among young children. To determine the effect of polysaccharide serogroup A vaccine for preventing serogroup A meningococcal meningitis. MEDLINE and the Cochrane Controlled Trials Register. The first stage of the review included prospective controlled trials. The second stage included non-experimental studies that addressed questions unanswered by the trials, i.e. the duration of protection and the effect of a booster dose in children under 2 years of age. One reviewer assessed the methodological quality of the trials, and two reviewers independently identified and assessed the non-experimental studies. Data from the trials were pooled using the Exact method to assess vaccine efficacy at 1, 2 and 3 years post- vaccination. The protective effect within the first year was consistent across all 8 trials, vaccine efficacy was 95% (Exact 95% CI 87%, 99%). Protection extended into the second and third year after vaccination, but the results did not attain statistical significance. The only trial that assessed the effect of a booster dose in children less than 18 months old, lacked adequate statistical power. In the three other trials that included children less than 6 years old (one in Sudan and two in Nigeria), none of the vaccinated children developed meningitis, but the results did not attain statistical significance. Data from the two non-experimental studies included in this review were not pooled with the trial data because of methodological limitations. For the first year after vaccination, the vaccine was strongly protective in participants over 5 years of age. It was also protective beyond the first year after vaccination, but the level of vaccine efficacy could not be determined with precision. Children aged 1 to 5 years in developing

IRIS Toxicological Review of Hexahydro-1,3,5-Trinitro-1,3,5 ...

EPA Pesticide Factsheets

On March 10, 2016, the public comment draft Toxicological Review of Hexahydro-1,3,5-trinitro-1,3,5-triazine and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Hexahydro-1,3,5-trinitro-1,3,5-triazine and the charge to external peer reviewers, are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for RDX. The outcome of this project is an updated Toxicological Review and IRIS Summary for RDX that will be entered into the IRIS database.

STS_135_Return

NASA Image and Video Library

2011-07-22

JSC2011-E-068761 (22 July 2011) --- A small portion of a large Ellington Field crowd is seen on July 22, 2011 through a door bearing a STS-135 sticker on its window. A short while later the crew of the space shuttle Atlantis' mission used this door for its entrance during a welcome home ceremony. STS-135 is the final mission of the NASA Space Shuttle Program. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Landing

NASA Image and Video Library

2011-07-21

JSC2011-E-067995 (21 July 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, makes a public statement as, from left, NASA Administrator Charles Bolden, along with NASA astronauts Rex Walheim, Sandy Magnus and Doug Hurley look on after the space shuttle Atlantis landed on July 21 at the Kennedy Space Center in Florida. The landing completed STS-135, the final mission of the NASA Space Shuttle Program. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

14 CFR 121.135 - Manual contents.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Manual contents. 121.135 Section 121.135 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS..., FLAG, AND SUPPLEMENTAL OPERATIONS Manual Requirements § 121.135 Manual contents. (a) Each manual...

33 CFR 175.135 - Existing equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Existing equipment. 175.135 Section 175.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.135 Existing equipment. Launchers...

33 CFR 175.135 - Existing equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Existing equipment. 175.135 Section 175.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.135 Existing equipment. Launchers...

33 CFR 175.135 - Existing equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Existing equipment. 175.135 Section 175.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.135 Existing equipment. Launchers...

33 CFR 175.135 - Existing equipment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Existing equipment. 175.135 Section 175.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.135 Existing equipment. Launchers...

33 CFR 175.135 - Existing equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Existing equipment. 175.135 Section 175.135 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.135 Existing equipment. Launchers...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...

22 CFR 135.44 - Termination for convenience.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Termination for convenience. 135.44 Section 135.44 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS..., Retention, and Enforcement § 135.44 Termination for convenience. Except as provided in § 135.43 awards may...

22 CFR 135.22 - Allowable costs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Allowable costs. 135.22 Section 135.22 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 135.22 Allowable...

22 CFR 135.22 - Allowable costs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Allowable costs. 135.22 Section 135.22 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 135.22 Allowable...

22 CFR 135.22 - Allowable costs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Allowable costs. 135.22 Section 135.22 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 135.22 Allowable...

22 CFR 135.22 - Allowable costs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Allowable costs. 135.22 Section 135.22 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 135.22 Allowable...

29 CFR 1910.135 - Head protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 5 2012-07-01 2012-07-01 false Head protection. 1910.135 Section 1910.135 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Personal Protective Equipment § 1910.135 Head protection. (a) General...

STS_135_Launch

NASA Image and Video Library

2011-07-08

JSC2011-E-067589 (8 July 2011) --- The space shuttle Atlantis launches for the STS-135 mission to the International Space Station in the final mission of the Space Shuttle Program at NASA?s Kennedy Space Center in Florida. Liftoff was at 11:29 a.m. (EDT) on July 8, 2011. Onboard are NASA astronauts Chris Ferguson, STS-135 commander; Doug Hurley, pilot; Sandy Magnus and Rex Walheim, both mission specialists. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Launch

NASA Image and Video Library

2011-07-09

JSC2011-E-067644 (8 July 2011) --- The space shuttle Atlantis launches for the STS-135 mission to the International Space Station in the final mission of the Space Shuttle Program at NASA?s Kennedy Space Center in Florida. Liftoff was at 11:29 a.m. (EDT) on July 8, 2011. Onboard are NASA astronauts Chris Ferguson, STS-135 commander; Doug Hurley, pilot; Sandy Magnus and Rex Walheim, both mission specialists. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Launch

NASA Image and Video Library

2011-07-08

JSC2011-E-067612 (8 July 2011) --- The space shuttle Atlantis launches for the STS-135 mission to the International Space Station in the final mission of the Space Shuttle Program at NASA?s Kennedy Space Center in Florida. Liftoff was at 11:29 a.m. (EDT) on July 8, 2011. Onboard are NASA astronauts Chris Ferguson, STS-135 commander; Doug Hurley, pilot; Sandy Magnus and Rex Walheim, both mission specialists. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Launch

NASA Image and Video Library

2011-07-08

JSC2011-E-067590 (8 July 2011) --- The space shuttle Atlantis launches for the STS-135 mission to the International Space Station in the final mission of the Space Shuttle Program at NASA?s Kennedy Space Center in Florida. Liftoff was at 11:29 a.m. (EDT) on July 8, 2011. Onboard are NASA astronauts Chris Ferguson, STS-135 commander; Doug Hurley, pilot; Sandy Magnus and Rex Walheim, both mission specialists. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Launch

NASA Image and Video Library

2011-07-09

JSC2011-E-067640 (8 July 2011) --- The space shuttle Atlantis launches for the STS-135 mission to the International Space Station in the final mission of the Space Shuttle Program at NASA?s Kennedy Space Center in Florida. Liftoff was at 11:29 a.m. (EDT) on July 8, 2011. Onboard are NASA astronauts Chris Ferguson, STS-135 commander; Doug Hurley, pilot; Sandy Magnus and Rex Walheim, both mission specialists. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

33 CFR 135.307 - Notification contents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Notification contents. 135.307 Section 135.307 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Notification of Pollution Incidents § 135.307...

47 CFR 24.135 - Frequency stability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Frequency stability. 24.135 Section 24.135... SERVICES Narrowband PCS § 24.135 Frequency stability. (a) The frequency stability of the transmitter shall... battery operated equipment, the equipment tests shall be performed using a new battery without any further...

47 CFR 24.135 - Frequency stability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Frequency stability. 24.135 Section 24.135... SERVICES Narrowband PCS § 24.135 Frequency stability. (a) The frequency stability of the transmitter shall... battery operated equipment, the equipment tests shall be performed using a new battery without any further...

47 CFR 24.135 - Frequency stability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Frequency stability. 24.135 Section 24.135... SERVICES Narrowband PCS § 24.135 Frequency stability. (a) The frequency stability of the transmitter shall... battery operated equipment, the equipment tests shall be performed using a new battery without any further...

47 CFR 24.135 - Frequency stability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Frequency stability. 24.135 Section 24.135... SERVICES Narrowband PCS § 24.135 Frequency stability. (a) The frequency stability of the transmitter shall... battery operated equipment, the equipment tests shall be performed using a new battery without any further...

47 CFR 24.135 - Frequency stability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Frequency stability. 24.135 Section 24.135... SERVICES Narrowband PCS § 24.135 Frequency stability. (a) The frequency stability of the transmitter shall... battery operated equipment, the equipment tests shall be performed using a new battery without any further...

34 CFR 300.135 - Written affirmation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Written affirmation. 300.135 Section 300.135 Education....135 Written affirmation. (a) When timely and meaningful consultation, as required by § 300.134, has occurred, the LEA must obtain a written affirmation signed by the representatives of participating private...

12 CFR 13.5 - Customer information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Customer information. 13.5 Section 13.5 Banks... PRACTICES § 13.5 Customer information. Prior to the execution of a transaction recommended to a non... obtain information concerning: (a) The customer's financial status; (b) The customer's tax status; (c...

22 CFR 135.41 - Financial reporting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Financial reporting. 135.41 Section 135.41... Enforcement § 135.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when letters...

23 CFR 1.35 - Bonus program.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Bonus program. 1.35 Section 1.35 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GENERAL MANAGEMENT AND ADMINISTRATION GENERAL § 1.35 Bonus program. (a) Any agreement entered into by a State pursuant to the provisions of section 12 of the...

23 CFR 1.35 - Bonus program.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Bonus program. 1.35 Section 1.35 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GENERAL MANAGEMENT AND ADMINISTRATION GENERAL § 1.35 Bonus program. (a) Any agreement entered into by a State pursuant to the provisions of section 12 of the...

23 CFR 1.35 - Bonus program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Bonus program. 1.35 Section 1.35 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GENERAL MANAGEMENT AND ADMINISTRATION GENERAL § 1.35 Bonus program. (a) Any agreement entered into by a State pursuant to the provisions of section 12 of the...

23 CFR 1.35 - Bonus program.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Bonus program. 1.35 Section 1.35 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GENERAL MANAGEMENT AND ADMINISTRATION GENERAL § 1.35 Bonus program. (a) Any agreement entered into by a State pursuant to the provisions of section 12 of the...

20 CFR 401.135 - Other laws.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Other laws. 401.135 Section 401.135 Employees' Benefits SOCIAL SECURITY ADMINISTRATION PRIVACY AND DISCLOSURE OF OFFICIAL RECORDS AND INFORMATION Disclosure of Official Records and Information § 401.135 Other laws. When the FOIA does not apply, we may not...

20 CFR 401.135 - Other laws.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Other laws. 401.135 Section 401.135 Employees' Benefits SOCIAL SECURITY ADMINISTRATION PRIVACY AND DISCLOSURE OF OFFICIAL RECORDS AND INFORMATION Disclosure of Official Records and Information § 401.135 Other laws. When the FOIA does not apply, we may not...

20 CFR 401.135 - Other laws.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Other laws. 401.135 Section 401.135 Employees' Benefits SOCIAL SECURITY ADMINISTRATION PRIVACY AND DISCLOSURE OF OFFICIAL RECORDS AND INFORMATION Disclosure of Official Records and Information § 401.135 Other laws. When the FOIA does not apply, we may not...

20 CFR 401.135 - Other laws.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Other laws. 401.135 Section 401.135 Employees' Benefits SOCIAL SECURITY ADMINISTRATION PRIVACY AND DISCLOSURE OF OFFICIAL RECORDS AND INFORMATION Disclosure of Official Records and Information § 401.135 Other laws. When the FOIA does not apply, we may not...

10 CFR 26.135 - Split specimens.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Split specimens. 26.135 Section 26.135 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.135 Split specimens. (a) If the FFD program follows split-specimen procedures, as described in § 26.113, the licensee testing...

10 CFR 26.135 - Split specimens.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Split specimens. 26.135 Section 26.135 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.135 Split specimens. (a) If the FFD program follows split-specimen procedures, as described in § 26.113, the licensee testing...

20 CFR 401.135 - Other laws.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Other laws. 401.135 Section 401.135 Employees' Benefits SOCIAL SECURITY ADMINISTRATION PRIVACY AND DISCLOSURE OF OFFICIAL RECORDS AND INFORMATION Disclosure of Official Records and Information § 401.135 Other laws. When the FOIA does not apply, we may not...

10 CFR 26.135 - Split specimens.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Split specimens. 26.135 Section 26.135 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.135 Split specimens. (a) If the FFD program follows split-specimen procedures, as described in § 26.113, the licensee testing...

10 CFR 26.135 - Split specimens.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Split specimens. 26.135 Section 26.135 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.135 Split specimens. (a) If the FFD program follows split-specimen procedures, as described in § 26.113, the licensee testing...

10 CFR 26.135 - Split specimens.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Split specimens. 26.135 Section 26.135 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.135 Split specimens. (a) If the FFD program follows split-specimen procedures, as described in § 26.113, the licensee testing...

22 CFR 135.41 - Financial reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Financial reporting. 135.41 Section 135.41... Enforcement § 135.41 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of...) Submitting financial reports to Federal agencies, or (ii) Requesting advances or reimbursements when letters...

KC-135 on ramp

NASA Technical Reports Server (NTRS)

1958-01-01

The Boeing KC-135 Stratotanker, besides being used extensively in its primary role as an inflight aircraft refueler, has assisted in several projects at the NASA Dryden Flight Research Center, Edwards, California. In 1957 and 1958, Dryden was asked by what was then the Civil Aeronautics Administration (later absorbed into the Federal Aviation Administration (FAA) in 1958) to help establish new approach procedure guidelines on cloud-ceiling and visibility minimums for Boeing's first jet airliner, the B-707. Dryden used a KC-135 (the military variant of the 707), seen here on the runway at Edwards Air Force Base, to aid the CAA in these tests. In 1979 and 1980, Dryden was again involved with general aviation research with the KC-135. This time, a special wingtip 'winglet', developed by Richard Whitcomb of Langley Research Center, was tested on the jet aircraft. Winglets are small, nearly vertical fins installed on an airplane's wing tips to help produce a forward thrust in the vortices that typically swirl off the end of the wing, thereby reducing drag. This winglet idea was tested at the Dryden Flight Research Center on a KC-135A tanker loaned to NASA by the Air Force. The research showed that the winglets could increase an aircraft's range by as much as 7 percent at cruise speeds. The first application of NASA's winglet technology in industry was in general aviation business jets, but winglets are now being incorporated into most new commercial and military transport jets, including the Gulfstream III and IV business jets, the Boeing 747-400 and MD-11 airliners, and the C-17 military transport. In the 1980's, a KC-135 was used in support of the Space Shuttle program. Since the Shuttle was to be launched from Florida, researchers wanted to test the effect of rain on the sensitive thermal tiles. Tiles were mounted on special fixtures on an F-104 aircraft and a P-3 Orion. The F-104 was flown in actual rain conditions, and also behind the KC-135 spray tanker as it

Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study.

PubMed

Klein, Nicola P; Habanec, Tomas; Kosina, Pavel; Shah, Nirmish R; Kolhe, Devayani; Miller, Jacqueline M; Hezareh, Marjan; Van der Wielen, Marie

2018-04-19

Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population. This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group). We measured immune responses to MenACWY-TT by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement and in terms of antibodies against polysaccharides of the 4 vaccine serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from pre-vaccination levels or titers ≥1:32 (rSBA)/≥1:8 (hSBA). We recorded solicited and unsolicited adverse events (AEs) during 4 and 31 days post-vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs) throughout the study. The according-to-protocol cohort for immunogenicity included 40 participants per group. In both groups, the first MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across vaccine serogroups. Following the second MenACWY-TT dose, all participants had high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups. rSBA and hSBA geometric mean titers for each serogroup increased in both groups (with different magnitudes, but ≥13.1-fold) compared with baseline levels. Polysaccharide antibody concentrations ≥2.0 μg/ml were detected in ≥84.4% of participants and were similar between groups. Incidences of solicited and unsolicited AEs were comparable between groups. We recorded SAEs in 4/43 participants in the high-risk group and 1/43 participants in the control group (none vaccine-related). No NOCIs were reported. In this descriptive study, MenACWY-TT induced similar functional and humoral immune responses and had a clinically

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.

PubMed

Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Karadag Oncel, Eda; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

2014-01-01

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey

PubMed Central

Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Oncel, Eda Karadag; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

2014-01-01

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. PMID:25483487

Increased Vaccination Coverage among Adolescents and Young Adults in the District of Palermo as a Result of a Public Health Strategy to Counteract an 'Epidemic Panic'.

PubMed

Costantino, Claudio; Restivo, Vincenzo; Ventura, Gianmarco; D'Angelo, Claudio; Randazzo, Maria Angela; Casuccio, Nicolò; Palermo, Mario; Casuccio, Alessandra; Vitale, Francesco

2018-05-17

During the summer of 2016 four cases of invasive meningococcal disease in rapid succession among young adults in the district of Palermo, Italy, resulting in one death, were widely reported by local and national mass media. The resultant 'epidemic panic' among the general population overloaded the vaccination units of the Palermo district over the following months. Strategies implemented by the Sicilian and local public health authorities to counteract 'meningitis fear' included the following: (a) extension of active and free-of-charge anti-meningococcal tetravalent vaccination from age class 12⁻18 to 12⁻30 years old; (b) implementation of vaccination units during normal clinic hours in rooms tailored for vaccine administration; (c) development of informative institutional tools and timely communication throughout local mass media to reassure the general population. In 2016, an increase in the anti-meningococcal coverage was observed in the Palermo district (+18% for 16-year-olds and +14% for 18-year-olds) and at the regional level (+11.2% and +13.5%, respectively). Concurrent catch-up of other recommended vaccinations for age (diphtheria-tetanus-pertussis-poliomyelitis and papillomavirus) resulted in a further increase of administered doses. The fear of meningitis, managed by the Sicilian public health authorities, had positive impacts in terms of prevention. In particular, the communication strategies that were adopted contributed to educating Sicilian young adults about vaccination issues.

31 CFR 1.35 - Information forms.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Information forms. 1.35 Section 1.35... § 1.35 Information forms. (a) Review of forms. Except for forms developed and used by constituent... developed and used by the Department of the Treasury to collect information from and about individuals. The...

STS_135_ MEDIA

NASA Image and Video Library

2011-06-30

JSC2011-E-060794 (30 June 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, points to acknowledge a reporter while greeting the media along with NASA astronauts Doug Hurley, pilot, and Sandy Magnus and Rex Walheim, both mission specialists, during the STS-135 crew media briefing at NASA?s Johnson Space Center June 30, 2011. The press conference provided the last scheduled opportunity for a large group of press to speak with the crew before the final launch on July 8. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

21 CFR 135.160 - Water ices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Water ices. 135.160 Section 135.160 Food and Drugs... CONSUMPTION FROZEN DESSERTS Requirements for Specific Standardized Frozen Desserts § 135.160 Water ices. (a) Description. Water ices are the foods each of which is prepared from the same ingredients and in the same...

21 CFR 135.160 - Water ices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Water ices. 135.160 Section 135.160 Food and Drugs... CONSUMPTION FROZEN DESSERTS Requirements for Specific Standardized Frozen Desserts § 135.160 Water ices. (a) Description. Water ices are the foods each of which is prepared from the same ingredients and in the same...

46 CFR 133.135 - Rescue boats.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST... Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156 and equipped as specified in table 133.175 of this...

46 CFR 133.135 - Rescue boats.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST... Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156 and equipped as specified in table 133.175 of this...

46 CFR 133.135 - Rescue boats.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST... Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.056 and equipped as specified in table 133.175 of this...

46 CFR 133.135 - Rescue boats.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST... Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156 and equipped as specified in table 133.175 of this...

46 CFR 133.135 - Rescue boats.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST... Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156 and equipped as specified in table 133.175 of this...

21 CFR 135.160 - Water ices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Water ices. 135.160 Section 135.160 Food and Drugs... CONSUMPTION FROZEN DESSERTS Requirements for Specific Standardized Frozen Desserts § 135.160 Water ices. (a) Description. Water ices are the foods each of which is prepared from the same ingredients and in the same...

21 CFR 135.160 - Water ices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Water ices. 135.160 Section 135.160 Food and Drugs... CONSUMPTION FROZEN DESSERTS Requirements for Specific Standardized Frozen Desserts § 135.160 Water ices. (a) Description. Water ices are the foods each of which is prepared from the same ingredients and in the same...

21 CFR 135.160 - Water ices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Water ices. 135.160 Section 135.160 Food and Drugs... CONSUMPTION FROZEN DESSERTS Requirements for Specific Standardized Frozen Desserts § 135.160 Water ices. (a) Description. Water ices are the foods each of which is prepared from the same ingredients and in the same...

KC-135 and Other Microgravity Simulations

NASA Technical Reports Server (NTRS)

2005-01-01

This document represents a summary of medical and scientific evaluations conducted aboard the KC-135 from June 23, 2004 to June 27, 2005. Included is a general overview of KC-135 activities manifested and coordinated by the Human Adaptation and Countermeasures Office. A collection of brief reports that describe tests conducted aboard the KC-135 follows the overview. Principal investigators and test engineers contributed significantly to the content of the report describing their particular experiment or hardware evaluation. This document concludes with an appendix that provides background information concerning the KC-135 and the Reduced-Gravity Program.

33 CFR 135.201 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Applicability. 135.201 Section 135.201 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.201 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Applicability. 135.201 Section 135.201 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.201 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Applicability. 135.201 Section 135.201 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.215 - Certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Certification. 135.215 Section 135.215 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.215 - Certification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Certification. 135.215 Section 135.215 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.215 - Certification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Certification. 135.215 Section 135.215 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.201 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Applicability. 135.201 Section 135.201 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.215 - Certification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Certification. 135.215 Section 135.215 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.201 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Applicability. 135.201 Section 135.201 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

33 CFR 135.215 - Certification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Certification. 135.215 Section 135.215 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND...

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus.

PubMed

Lujan-Zilbermann, Jorge; Warshaw, Meredith G; Williams, Paige L; Spector, Stephen A; Decker, Michael D; Abzug, Mark J; Heckman, Barb; Manzella, Adam; Kabat, Bill; Jean-Philippe, Patrick; Nachman, Sharon; Siberry, George K

2012-10-01

To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. Copyright © 2012 Mosby, Inc. All rights reserved.

7 CFR 966.135 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Appeals. 966.135 Section 966.135 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and...

IRIS Toxicological Review of Hexahydro-1,3,5-Trinitro-1,3,5 ...

EPA Pesticide Factsheets

EPA is developing an Integrated Risk Information System (IRIS) assessment of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and has released the draft assessment for public comment. When final, the assessment will appear on the IRIS database. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for RDX. The outcome of this project is an updated Toxicological Review and IRIS Summary for RDX that will be entered into the IRIS database.

Epidemiology and diagnostic testing for meningitis in adults as the meningococcal epidemic declined at Middlemore Hospital.

PubMed

McBride, Stephen; Fulke, Jennifer; Giles, Hannah; Hobbs, Mark; Suh, Jun; Sathyendran, Vani; Thompson, Emily; Taylor, Susan; Holland, David

2015-03-13

To describe changes in epidemiology and diagnostic techniques for adult meningitis at Middlemore Hospital following the decline of the meningococcal epidemic. Retrospective audit of cases of meningitis from 2000 to 2009. Microbiologically-confirmed diagnosis (MCD) was established in 296 of 743 episodes (40%), most commonly enterovirus (123/296, 42%), Neisseria meningitidis (43/296, 15%) and Streptococcus pneumoniae (34/296, 11%). N. meningitidis meningitis declined and herpes viruses increased over time, without significant change in overall meningitis case numbers. By 2009, S. pneumoniae constituted a greater proportion of cases than N. meningitidis. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and pneumococcal immunochromatographic testing (PICT) increased over time as did the proportion of cases with MCD. CSF Gram stain was positive in 45% (53/118) and CSF culture made MCD in 37% (44/118) of confirmed bacterial episodes (CBE). PCR provided MCD in 59% (26/54) of CBE and 99% (168/170) of viral episodes. CSF PICT was tested in 76% (26/34) of S. pneumoniae meningitis (positive in 92% (24/26). As the epidemic waned, local incidence of meningococcal meningitis decreased without significant decreasing meningitis overall. Empiric treatment for meningitis in New Zealand adults should routinely include pneumococcal cover. Increased PCR testing increases MCD in meningitis.

7 CFR 1956.131-1956.135 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true [Reserved] 1956.131-1956.135 Section 1956.131-1956.135...) PROGRAM REGULATIONS (CONTINUED) DEBT SETTLEMENT Debt Settlement-Community and Business Programs §§ 1956.131-1956.135 [Reserved] ...

Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

PubMed

Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2015-12-01

We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

STS_135_FDF

NASA Image and Video Library

2011-06-24

JSC2011-E-059611 (24 June 2011) --- NASA astronaut Sandy Magnus, STS-135 mission specialist, leans out around pilot Doug Hurley, left, to confer with commander Chris Ferguson (out of frame) as the crew of the final space shuttle mission participates in the STS-135 Flight Data File (FDF) review at NASA?s Johnson Space Center June 24, 2011. The review involves examining and annotating more than 200 procedure books and cue cards that comprise all of the detailed technical steps that will be performed during the mission. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

14 CFR 135.149 - Equipment requirements: General.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 135-1, 44 FR 26737, May 7, 1979; Amdt. 135-34, 54 FR 43926, Oct. 27, 1989; Amdt. 135-38, 55 FR 43310... REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Aircraft and...

14 CFR 135.149 - Equipment requirements: General.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... 135-1, 44 FR 26737, May 7, 1979; Amdt. 135-34, 54 FR 43926, Oct. 27, 1989; Amdt. 135-38, 55 FR 43310... REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Aircraft and...

14 CFR 135.149 - Equipment requirements: General.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... 135-1, 44 FR 26737, May 7, 1979; Amdt. 135-34, 54 FR 43926, Oct. 27, 1989; Amdt. 135-38, 55 FR 43310... REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Aircraft and...

14 CFR 135.149 - Equipment requirements: General.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... 135-1, 44 FR 26737, May 7, 1979; Amdt. 135-34, 54 FR 43926, Oct. 27, 1989; Amdt. 135-38, 55 FR 43310... REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Aircraft and...

14 CFR 135.149 - Equipment requirements: General.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... 135-1, 44 FR 26737, May 7, 1979; Amdt. 135-34, 54 FR 43926, Oct. 27, 1989; Amdt. 135-38, 55 FR 43310... REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Aircraft and...

50 CFR 86.135 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false [Reserved] 86.135 Section 86.135 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM How...

Clonal Distribution of Disease-Associated and Healthy Carrier Isolates of Neisseria meningitidis between 1983 and 2005 in Cuba ▿

PubMed Central

Climent, Yanet; Yero, Daniel; Martinez, Isabel; Martín, Alejandro; Jolley, Keith A.; Sotolongo, Franklin; Maiden, Martin C. J.; Urwin, Rachel; Pajón, Rolando

2010-01-01

In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST. PMID:20042619

Distribution of Serogroups and Genotypes among Disease-Associated and Carried Isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway

PubMed Central

Yazdankhah, Siamak P.; Kriz, Paula; Tzanakaki, Georgina; Kremastinou, Jenny; Kalmusova, Jitka; Musilek, Martin; Alvestad, Torill; Jolley, Keith A.; Wilson, Daniel J.; McCarthy, Noel D.; Caugant, Dominique A.; Maiden, Martin C. J.

2004-01-01

The distribution of serogroups and multilocus sequence types (STs) in collections of disease-associated and carried meningococci from the period 1991 to 2000 in three European countries (the Czech Republic, Greece, and Norway) was investigated. A total of 314 patient isolates and 353 isolates from asymptomatic carriers were characterized. The frequency distributions of serogroups and clone complexes differed among countries and between disease and carrier isolate collections. Highly significant differentiation was seen at each housekeeping locus. A marked positive association of serogroup C with disease was evidenced. The ST-11 complex was strongly positively associated with disease; associations for other clone complexes were weaker. The genetic diversity of the clone complexes differed. A single ST dominated the ST-11 clone complex, while the ST-41/44 complex exhibited greater levels of diversity. These data robustly demonstrated differences in the distribution of meningococcal genotypes in disease and carrier isolates and among countries. Further, they indicated that differences in genotype diversity and pathogenicity exist between meningococcal clone complexes. PMID:15528708

Public health action and mass chemoprophylaxis in response to a small meningococcal infection outbreak at a nursery in the West Midlands, England.

PubMed

Stewart, Antony; Coetzee, Nic; Knapper, Elizabeth; Rajanaidu, Subhadra; Iqbal, Zafar; Duggal, Harsh

2013-03-01

Meningococcal infection is fatal in 10% of cases, and age-specific attack rates are highest in infancy. A nursery outbreak was declared just before a bank holiday weekend in August 2010, when two children attending the same nursery were confirmed to have meningococcal infection. Although such outbreaks are rare, they generate considerable public alarm and are challenging to manage and control. This report describes the investigation and public health response to the outbreak. Both cases had relatively mild disease and were confirmed as having serogroup B infection. Chemoprophylaxis and advice were given to most of the 146 children and 30 staff at the nursery. Within 28 hours of declaring the outbreak, over 95% of parents received information, advice and prescriptions for their children. GPs were also given information and the after-hours service provided continuity over the weekend. No further cases were identified and the outbreak was closed four weeks after being declared. Considerable logistical challenges were involved in providing timely advice and chemoprophylaxis to the entire nursery and staff one day before a bank holiday weekend. The speed of the public health response and implementation of preventive measures was crucial in providing assurance to parents and staff, and reducing their anxiety. The decision to provide on-site prescribing at the nursery (coupled with information sessions and individual counselling) proved to be a key implementation-success factor. Effective coordination and management by the outbreak control team was able to rapidly provide leadership, delegate tasks, identify gaps, allocate resources and ensure a proactive media response. A number of useful lessons were learnt and recommendations were made for future local practice.

40 CFR 1037.135 - Labeling.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Labeling. 1037.135 Section 1037.135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF... identify other emission standards that the vehicle meets or does not meet (such as European standards). You...

40 CFR 1037.135 - Labeling.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Labeling. 1037.135 Section 1037.135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF... that the vehicle meets or does not meet (such as European standards). You may also add other...

40 CFR 1037.135 - Labeling.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Labeling. 1037.135 Section 1037.135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF... identify other emission standards that the vehicle meets or does not meet (such as European standards). You...

Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults.

PubMed

Konar, Monica; Granoff, Dan M

2017-08-17

Eculizumab, a humanized anti-complement C5 monoclonal antibody (mAb) for treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, blocks the terminal complement pathway required for serum bactericidal activity (SBA). Because treated patients are at >1000-fold increased risk of meningococcal disease, vaccination is recommended; whether vaccination can protect by opsonophagocytic activity in the absence of SBA is not known. Meningococci were added to anticoagulated blood from 12 healthy adults vaccinated with meningococcal serogroup B and serogroup A, C, W, Y vaccines. Bacterial survival was measured after 3-hour incubation in the presence of eculizumab or control complement factor D inhibitor ACH-4471, which blocks the complement alternative pathway (AP) and is in phase 2 development for treatment of PNH. In the absence of inhibitors, colony formation units (CFUs) per milliliter in blood from all 12 immunized subjects decreased from ∼4000 at time 0 to sterile cultures at 3 hours. In the presence of eculizumab, there was a >22-fold increase in geometric mean CFUs per milliliter (90 596 and 114 683 CFU/mL for serogroup B and C strains, respectively; P < .0001 compared with time 0). In the presence of ACH-4471, there was a >12-fold decrease (23 and 331 CFU/mL, respectively; P < .0001). The lack of meningococci killing by blood containing eculizumab resulted from inhibition of release of C5a, a C5 split product needed for upregulation of phagocytosis. The results provide an explanation for the large number of cases of meningococcal disease in immunized patients being treated with eculizumab and suggest that vaccination may provide better protection against meningococcal disease in patients treated with an AP-specific inhibitor. © 2017 by The American Society of Hematology.

KC-135 and Other Microgravity Simulations

NASA Technical Reports Server (NTRS)

Skinner, Noel C.

1999-01-01

This document represents a summary of medical and scientific evaluations conducted aboard the KC-135 from June 20, 1998 to June 20, 1999. Included is a general overview of KC-135 activities manifested and coordinated by the Life Sciences Research Laboratories. A collection of brief reports that describes tests conducted aboard the KC-135 follows the overview. Principal investigators and test engineers contributed significantly to the content of the report describing their particular experiment or hardware evaluation. Although this document follows general guidelines, each report format may vary to accommodate differences in experiment design and procedures. This document concludes with an appendix that provides background information concerning the KC-135 and the Reduced-Gravity Program.

KC-135 and Other Microgravity Simulations

NASA Technical Reports Server (NTRS)

Skinner, Noel C.; Schlegel, Todd T. (Technical Monitor)

2001-01-01

This document represents a summary of medical and scientific evaluations conducted aboard the KC-135 from January to June 15, 2001. Included is a general overview of KC-135 activities manifested and coordinated by the Human Adaptation and Countermeasures Office. A collection of brief reports that describes tests conducted aboard the KC-135 follows the overview. Principal investigators and test engineers contributed significantly to the content of the report describing their particular experiment or hardware evaluation. Although this document follows general guidelines, each report format may vary to accommodate differences in experiment design and procedures. This document concludes with an appendix that provides background information concerning the KC-135 and the Reduced-Gravity Program.

14 CFR 135.203 - VFR: Minimum altitudes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false VFR: Minimum altitudes. 135.203 Section 135.203 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.203 VFR: Minimum altitudes. Except when necessary for...

14 CFR 135.205 - VFR: Visibility requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false VFR: Visibility requirements. 135.205 Section 135.205 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Operating Limitations and Weather Requirements § 135.205 VFR: Visibility requirements. (a) No person may...

14 CFR 135.215 - IFR: Operating limitations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false IFR: Operating limitations. 135.215 Section 135.215 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.215 IFR: Operating limitations. (a) Except as provided...