[Invasive meningococcal disease in Navarra in the era of a meningococcal C vaccine].

Science.gov (United States)

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

2017-04-01

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

Epidemiology of invasive meningococcal B disease in Australia, 1999-2015: priority populations for vaccination.

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Archer, Brett N; Chiu, Clayton K; Jayasinghe, Sanjay H; Richmond, Peter C; McVernon, Jodie; Lahra, Monica M; Andrews, Ross M; McIntyre, Peter B

2017-11-06

To describe trends in the age-specific incidence of serogroup B invasive meningococcal disease (IMD) in Australia, 1999-2015. Analysis in February 2017 of de-identified notification data from the Australian National Notifiable Diseases Surveillance System of all notifications of IMD in Australia with a recorded diagnosis date during 1999-2015.Major outcomes: IMD notification rates in Australia, 1999-2015, by age, serogroup, Indigenous status, and region. The incidence of meningococcal serogroup B (MenB) disease declined progressively from 1.52 cases per 100 000 population in 2001 to 0.47 per 100 000 in 2015. During 2006-2015, MenB accounted for 81% of IMD cases with a known serogroup; its highest incidence was among infants under 12 months of age (11.1 [95% CI, 9.81-12.2] per 100 000), children aged 1-4 years (2.82 [95% CI, 2.52-3.15] per 100 000), and adolescents aged 15-19 years (2.40 [95% CI, 2.16-2.67] per 100 000). Among the 473 infants under 2 years of age with MenB, 43% were under 7 months and 69% under 12 months of age. The incidence of meningococcal serogroup C (MenC) disease prior to the introduction of the MenC vaccine in 2003 was much lower in infants than for MenB (2.60 cases per 100 000), the rate peaking in people aged 15-19 years (3.32 per 100 000); the overall case fatality rate was also higher (MenC, 8%; MenB, 4%). The incidence of MenB disease was significantly higher among Indigenous than non-Indigenous Australians during 2006-2015 (incidence rate ratio [IRR], 3.8; 95% CI, 3.3-4.5). Based on disease incidence at its current low endemic levels, priority at risk age/population groups for MenB vaccination include all children between 2 months and 5 years of age, Indigenous children under 10 years of age, and all adolescents aged 15-19 years. Given marked variation in meningococcal disease trends over time, close scrutiny of current epidemiologic data is essential.

Invasive meningococcal disease without meningitis: a forgotten diagnosis

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Walayat S

2018-04-01

Full Text Available Saqib Walayat,1 Nooreen Hussain,1 Abdullah H Malik,1 Elsa Vazquez-Melendez,1 Bhagat S Aulakh,2 Teresa Lynch1 1Department of Internal Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA; 2Department of Pulmonary/Critical Care Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA Abstract: Neisseria meningitidis, a Gram-negative diplococcus, is an uncommon cause of pneumonia. There have been only about 344 cases reported worldwide from 1906 to 2015. To our knowledge, there have been only 3 cases reported in the USA in the past 2 decades. We present a case of a 72-year-old male with a past medical history of severe COPD, obstructive sleep apnea, and stage I lung cancer status post-stereotactic body radiation therapy 1 year ago, who was admitted with a 6-day history of productive cough with yellowish sputum, shortness of breath, extreme myalgias, and fatigue. Chest X-ray revealed an infiltrative process in the left lower lung field and left-sided pleural effusion. Blood cultures grew beta-lactamase-negative N. meningitidis after 24 hours. Our patient was initially treated with broad-spectrum antibiotics, which were later switched to amoxicillin to complete a total of 14 days of antibiotics. Diagnosing meningococcal pneumonia requires a high level of suspicion, as sputum cultures may be falsely positive due to asymptomatic carriage of the organism in the upper respiratory tract in up to 10% of outpatient population. We highlight this case as early recognition and treatment is critical. The case fatality rate for N. meningitidis pneumonia has been reported to be higher compared with meningococcal meningitis. Keywords: Neisseria meningitidis, pneumonia, invasive meningococcal pneumonia, sepsis

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

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Raymond S.W. Tsang

2018-04-01

Full Text Available Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

Consensus recommendation for meningococcal disease prevention for Hajj and Umra pilgrimage/travel medicine.

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Shibl, A; Tufenkeji, H; Khalil, M; Memish, Z

2013-04-01

The Islamic Hajj to Makkah (Mecca) has been associated with outbreaks of invasive meningococcal disease and the global spread of Neisseria meningitidis serogroup W-135. For Hajj pilgrims the quadrivalent vaccination against serogroups A, C, W-135 and Y is a mandatory requirement. Novel conjugate vaccines may provide benefits for the community by reduction of carriage. With the introduction of the new generation of quadrivalent meningococcal conjugate vaccines (Menveo, Menactra, and others pending license) and their recent implementation in Saudi Arabia, experts from 11 countries in the Middle East region met at a Meningococcal Leadership Forum (MLF), in Dubai in May 2010 to exchange opinions on meningococcal disease and prevention strategies. These experts discussed the importance of introducing conjugate vaccines for pilgrims and travellers, and elaborated a consensus recommendation to support healthcare professionals and decision-makers.

Acute meningococcal disease in children and adolescents

DEFF Research Database (Denmark)

Nygaard, Ulrikka; Vissing, Nadja Hawwa; Steensen, Morten

2017-01-01

Meningococcal disease is a rapidly progressing infection, which continues to cause deaths among children and adolescents. In this review, clinical signs and initial treatment of acute childhood meningococcal disease is described. Operational flow charts have been developed for assessment of non......-blanching rash and initial treatment of meningococcal disease....

Changing epidemiology of Infant Meningococcal Disease after the introduction of meningococcal serogroup C vaccine in Italy, 2006-2014.

Science.gov (United States)

Stefanelli, P; Fazio, C; Neri, A; Boros, S; Renna, G; Pompa, M G

2015-07-17

In Italy, the incidence of Invasive Meningococcal Disease (IMD) was around 0.28 per 100,000 over the last years. Since the risk IMD is usually high among infants aged less than 1 year, we decided to evaluate the trend of IMD cases reported between 2006 and 2014 in this age group. In particular, the study aim was to describe the main characteristics of IMD cases in infants following the introduction of MCC vaccine (2005) and to estimate the number of cases which are potentially preventable through early vaccination. The National Surveillance System of Bacterial Meningitis was established in 1994 and in 2007 was extended to all invasive bacterial diseases. Clinical data and isolates and/or clinical samples are collected from hospitalized patients throughout the country. IMD cases are reported by clinicians to the local health authorities, and samples are sent to the Reference Laboratory at the Istituto Superiore di Sanità for further characterization and storage at -80°C. In particular, serogroup identification is obtained by agglutination with commercial antisera or by multiplex PCR. The annual incidence for infants B was more frequently detected among infants aged B was the most commonly detected over time. The long-term impact of meningococcal C conjugate vaccine and the effect of the introduction of meningococcal B vaccination among infants need to be evaluated. Copyright © 2015 Elsevier Ltd. All rights reserved.

The meningococcal antibody test: how useful in the diagnosis of meningococcal disease?

DEFF Research Database (Denmark)

Weis, N; Berthelsen, L; Wachmann, H

2005-01-01

Based on 9257 [correction] blood samples received from 7365 patients with a request for a meningococcal antibody test (MAT) during a 10-year period (1986-1995), the usefulness of the test in the diagnosis of meningococcal disease was assessed. Of 635 patients with culture-confirmed meningococcal ...

The next chapter for group B meningococcal vaccines.

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Wang, N Y; Pollard, A J

2018-02-01

The majority of invasive meningococcal disease (IMD) in the developed world is caused by capsular group B Neisseria meningitidis, however success with vaccination against organisms bearing this capsule has previously been restricted to control of geographically limited clonal outbreaks. As we enter a new era, with the first routine program underway to control endemic group B meningococcal disease for infants in the UK, it is timely to review the key landmarks in group B vaccine development, and discuss the issues determining whether control of endemic group B disease will be achieved. Evidence of a reduction in carriage acquisition of invasive group B meningococcal strains, after vaccination among adolescents, is imperative if routine immunization is to drive population control of disease beyond those who are vaccinated (i.e. through herd immunity). The need for multiple doses to generate a sufficiently protective response and reactogenicity remain significant problems with the new generation of vaccines. Despite these limitations, early data from the UK indicate that new group B meningococcal vaccines have the potential to have a major impact on meningococcal disease, and to provide new insight into how we might do better in the future.

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

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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.

Meningococcal B Vaccine Failure With a Penicillin-Resistant Strain in a Young Adult on Long-Term Eculizumab.

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Parikh, Sydel R; Lucidarme, Jay; Bingham, Coralie; Warwicker, Paul; Goodship, Tim; Borrow, Ray; Ladhani, Shamez N

2017-09-01

We describe a case of invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant strain in a fully immunized young adult on long-term complement inhibitor therapy and daily penicillin chemoprophylaxis. Eculizumab is a humanized monoclonal antibody that binds human complement C5 protein and inhibits the terminal complement pathway. It is currently recommended for the treatment of complement-mediated thrombotic microangiopathies. An unwanted complication of inhibiting complement, however, is an increased risk of invasive meningococcal disease. Here, we report the first case of meningococcal group B vaccine failure in a young adult receiving eculizumab for atypical hemolytic uremic syndrome. She developed invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant meningococcal group B strain 4 months after receiving 2 doses of meningococcal group B vaccine while on oral penicillin prophylaxis against meningococcal infection. Copyright © 2017 by the American Academy of Pediatrics.

Acute meningococcal disease in children and adolescents

DEFF Research Database (Denmark)

Nygaard, Ulrikka; Vissing, Nadja Hawwa; Steensen, Morten

2017-01-01

Meningococcal disease is a rapidly progressing infection, which continues to cause deaths among children and adolescents. In this review, clinical signs and initial treatment of acute childhood meningococcal disease is described. Operational flow charts have been developed for assessment of non...

Prospects for eradication of meningococcal disease

OpenAIRE

Nadel, Simon

2012-01-01

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

Does Dexamethasone Helps in Meningococcal Sepsis?

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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.

Does Dexamethasone Helps in Meningococcal Sepsis?

Science.gov (United States)

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

Can we control all-cause meningococcal disease in Europe?

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Sadarangani, M; Pollard, A J

2016-12-01

Invasive disease caused by Neisseria meningitidis is potentially devastating, with a case fatality rate of 5-15% and high rates of significant sequelae among survivors after septicaemia or meningitis. Capsular group C (MenC) conjugate vaccines have been highly successful in achieving control of MenC disease across Europe, and some countries have also introduced quadrivalent MenACWY conjugate vaccines to reduce disease caused by groups A, W and Y in addition to C. These vaccines putatively elicit protective levels of bactericidal antibodies in all age groups, induce immunologic memory and reduce nasopharyngeal carriage, thereby leading to herd protection. Protein-based meningococcal vaccines based on subcapsular components, and designed primarily to target capsular group B (MenB) disease, have recently been licensed. These vaccines are highly immunogenic in infants and adolescents, inducing bactericidal antibodies against strains expressing high levels of vaccine antigens which are identical to the variants present in the vaccines. Effectiveness of these vaccines at a population level will be determined by whether vaccine-induced antibodies provide cross-protection against variants of the vaccine antigens present on the surface of the diverse collection of circulating invasive strains. The level of serum bactericidal activity induced against strains also seems to depend on the level of expression of the vaccine antigens. The duration of protection and the impact on carriage of meningococci will have a major bearing on the overall effectiveness of the programme. In September 2015 the UK became the first country to introduce the multicomponent meningococcal serogroup B vaccine (4CMenB) into a national routine immunization schedule, and data on the effectiveness of this programme are anticipated in the next few years. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

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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.

Upper respiratory tract infection, heterologous immunisation and meningococcal disease

NARCIS (Netherlands)

Scholten, R. J.; Bijlmer, H. A.; Tobi, H.; Dankert, J.; Bouter, L. M.

1999-01-01

To test the hypothesis that an episode of upper respiratory tract infection or heterologous immunisation is a predisposing factor for the occurrence of meningococcal disease, data from 377 cases of meningococcal disease and their household contacts (n = 1124) were analysed by conditional logistic

EpiScanGIS: an online geographic surveillance system for meningococcal disease

Directory of Open Access Journals (Sweden)

Albert Jürgen

2008-07-01

Full Text Available Abstract Background Surveillance of infectious diseases increasingly relies on Geographic Information Systems (GIS. The integration of pathogen fine typing data in dynamic systems and visualization of spatio-temporal clusters are a technical challenge for system development. Results An online geographic information system (EpiScanGIS based on open source components has been launched in Germany in May 2006 for real time provision of meningococcal typing data in conjunction with demographic information (age, incidence, population density. Spatio-temporal clusters of disease detected by computer assisted cluster analysis (SaTScan™ are visualized on maps. EpiScanGIS enables dynamic generation of animated maps. The system is based on open source components; its architecture is open for other infectious agents and geographic regions. EpiScanGIS is available at http://www.episcangis.org, and currently has 80 registered users, mostly from the public health service in Germany. At present more than 2,900 cases of invasive meningococcal disease are stored in the database (data as of June 3, 2008. Conclusion EpiScanGIS exemplifies GIS applications and early-warning systems in laboratory surveillance of infectious diseases.

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

Science.gov (United States)

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

2018-01-01

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. 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. 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). 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. 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. 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 reflection presents an innovative patient safety approach

European public health policies for managing contacts of invasive meningococcal disease cases better harmonised in 2013 than in 2007.

Science.gov (United States)

Vygen, Sabine; Hellenbrand, Wiebke; Stefanoff, Pawel; Hanquet, Germaine; Heuberger, Sigrid; Stuart, James

2016-01-01

In 2007, a European survey identified variation in country policies on public health management of invasive meningococcal disease (IMD). In 2009-10, the European Centre for Disease Prevention and Control (ECDC) published evidence-based guidance on IMD. We therefore surveyed again European countries to describe policies for managing IMD cases and contacts in 2013. We asked national IMD public health experts from 32 European countries to complete a questionnaire focusing on post-exposure prophylaxis (PEP) for IMD contacts and meningococcal vaccination. Proportions in 2007 and 2013 were compared using the chi-squared test. All 32 countries responded, with responses from two regions for Belgium and Italy; half stated having used ECDC guidance to update national recommendations. PEP was recommended to close contacts in 33 of 34 countries/regions, mainly ciprofloxacin for adults (29/32 countries) and rifampicin for children (29/32 countries). ECDC guidance for managing IMD contacts in airplanes was strictly followed by five countries/regions. Twenty-three countries/regions participated in both surveys. Compared with 2007, in 2013, more countries/regions recommended i) ceftriaxone for children (15/23 vs 6/20; p = 0.03), ii) PEP for all children in the same preschool group (8/23 vs 17/23; p = 0.02). More countries/regions recommended evidence-based measures for IMD public health management in 2013 than 2007. However, some discrepancies remain and they call for further harmonisation.

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

Science.gov (United States)

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.

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men

Science.gov (United States)

Taha, Muhamed-Kheir; Becher, Dörte; Deghmane, Ala-Eddine; Frosch, Matthias; Hellenbrand, Wiebke; Hong, Eva; Parent du Châtelet, Isabelle; Prior, Karola; Harmsen, Dag; Vogel, Ulrich

2016-01-01

Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract. PMID:27167067

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men.

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Muhamed-Kheir Taha

Full Text Available Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM. We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.

NNDSS - Table II. Meningococcal disease to Pertussis

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal disease to Pertussis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Lyme disease to Meningococcal

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Lyme disease to Meningococcal

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

Vaccines for prevention of group B meningococcal disease: Not your father's vaccines.

Science.gov (United States)

Harrison, Lee H

2015-11-27

For decades, there was no licensed vaccine for prevention of endemic capsular group B meningococcal disease, despite the availability of vaccines for prevention of the other most common meningococcal capsular groups. Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease. These issues are discussed in this review. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

Respiratory virus infection and risk of invasive meningococcal disease in central Ontario, Canada.

Directory of Open Access Journals (Sweden)

Ashleigh R Tuite

Full Text Available BACKGROUND: In temperate climates, invasive meningococcal disease (IMD incidence tends to coincide with or closely follow peak incidence of influenza virus infection; at a seasonal level, increased influenza activity frequently correlates with increased seasonal risk of IMD. METHODS: We evaluated 240 cases of IMD reported in central Ontario, Canada, from 2000 to 2006. Associations between environmental and virological (influenza A, influenza B and respiratory syncytial virus (RSV exposures and IMD incidence were evaluated using negative binomial regression models controlling for seasonal oscillation. Acute effects of weekly respiratory virus activity on IMD risk were evaluated using a matched-period case-crossover design with random directionality of control selection. Effects were estimated using conditional logistic regression. RESULTS: Multivariable negative binomial regression identified elevated IMD risk with increasing influenza A activity (per 100 case increase, incidence rate ratio = 1.18, 95% confidence interval (CI: 1.06, 1.31. In case-crossover models, increasing weekly influenza A activity was associated with an acute increase in the risk of IMD (per 100 case increase, odds ratio (OR  = 2.03, 95% CI: 1.28 to 3.23. Increasing weekly RSV activity was associated with increased risk of IMD after adjusting for RSV activity in the previous 3 weeks (per 100 case increase, OR = 4.31, 95% CI: 1.14, 16.32. No change in disease risk was seen with increasing influenza B activity. CONCLUSIONS: We have identified an acute effect of influenza A and RSV activity on IMD risk. If confirmed, these finding suggest that influenza vaccination may have the indirect benefit of reducing IMD risk.

Adolescent meningococcal serogroup A, W and Y immune responses following immunization with quadrivalent meningococcal A, C, W and Y conjugate vaccine : Optimal age for vaccination

NARCIS (Netherlands)

van Ravenhorst, Mariëtte B.; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A.M.; Berbers, Guy A M

2017-01-01

Background Recently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and

Adolescent meningococcal serogroup A, W and Y immune responses following immunization with quadrivalent meningococcal A, C, W and Y conjugate vaccine: Optimal age for vaccination.

NARCIS (Netherlands)

van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M

2017-01-01

Recently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and reduce

Susceptibility to invasive meningococcal disease: polymorphism of complement system genes and Neisseria meningitidis factor H binding protein.

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Declan T Bradley

Full Text Available Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH is associated with altered risk of invasive meningococcal disease (IMD. We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP affected the risk association.We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.Rs12085435 A in C8B was associated with odds ratio (OR of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction. A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10⁻⁴. There was no bacterial load (CtrA cycle threshold difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025.The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become

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

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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.

Meningococcal disease serogroup C

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Cuevas IE

2012-03-01

Full Text Available Félix O Dickinson1, Antonio E Pérez1, Iván E Cuevas21Department of Epidemiology, “Pedro Kourí” Institute, Havana, Cuba; 2Pharmacovigilance Group, Finlay Institute, Havana, CubaAbstract: Despite current advances in antibiotic therapy and vaccines, meningococcal disease serogroup C (MDC remains a serious threat to global health, particularly in countries in North and Latin America, Europe, and Asia. MDC is a leading cause of morbidity, mortality, and neurological sequelae and it is a heavy economic burden. At the individual level, despite advances in antibiotics and supportive therapies, case fatality rate remains nearly 10% and severe neurological sequelae are frequent. At the population level, prevention and control of infection is more challenging. The main approaches include health education, providing information to the public, specific treatment, chemoprophylaxis, and the use of vaccines. Plain and conjugate meningococcal C polysaccharide vaccines are considered safe, are well tolerated, and have been used successfully for over 30 years. Most high-income countries use vaccination as a part of public health strategies, and different meningococcal C vaccination schedules have proven to be effective in reducing incidence. This is particularly so with conjugate vaccines, which have been found to induce immunogenicity in infants (the age group with the highest incidence rates of disease, stimulate immunologic memory, have longer effects, not lead to hyporesponsiveness with repeated dosing, and decrease acquisition of nasopharyngeal carriage, inducing herd immunity. Antibiotics are considered a cornerstone of MDC treatment and must be administered empirically as soon as possible. The choice of which antibiotic to use should be made based on local antibiotic resistance, availability, and circulating strains. Excellent options for a 7-day course are penicillin, ampicillin, chloramphenicol, and third-generation cephalosporins (ceftriaxone and

Association of secondhand smoke exposure with pediatric invasive bacterial disease and bacterial carriage: a systematic review and meta-analysis.

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Chien-Chang Lee

2010-12-01

Full Text Available A number of epidemiologic studies have observed an association between secondhand smoke (SHS exposure and pediatric invasive bacterial disease (IBD but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis, Haemophilus influenzae type B (Hib, and Streptococcus pneumoniae (S. pneumoniae.Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52-2.69 for invasive meningococcal disease, 1.21 (95% CI 0.69-2.14 for invasive pneumococcal disease, and 1.22 (95% CI 0.93-1.62 for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19-2.36 for N. meningitidis, 1.66 (95% CI 1.33-2.07 for S. pneumoniae, and 0.96 (95% CI 0.48-1.95 for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72-6.13.When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be associated with invasive meningococcal disease. The

NNDSS - Table II. Lyme disease to Meningococcal

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U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2014In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases...

Vaccine prevention of meningococcal disease in Africa: Major advances, remaining challenges.

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Mustapha, Mustapha M; Harrison, Lee H

2017-12-06

Africa historically has had the highest incidence of meningococcal disease with high endemic rates and periodic epidemics. The meningitis belt, a region of sub-Saharan Africa extending from Senegal to Ethiopia, has experienced large, devastating epidemics. However, dramatic shifts in the epidemiology of meningococcal disease have occurred recently. For instance, meningococcal capsular group A (NmA) epidemics in the meningitis belt have essentially been eliminated by use of conjugate vaccine. However, NmW epidemics have emerged and spread across the continent since 2000; NmX epidemics have occurred sporadically, and NmC recently emerged in Nigeria and Niger. Outside the meningitis belt, NmB predominates in North Africa, while NmW followed by NmB predominate in South Africa. Improved surveillance is necessary to address the challenges of this changing epidemiologic picture. A low-cost, multivalent conjugate vaccine covering NmA and the emergent and prevalent meningococcal capsular groups C, W, and X in the meningitis belt is a pressing need.

Global epidemiology of capsular group W meningococcal disease (1970-2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex.

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Mustapha, Mustapha M; Marsh, Jane W; Harrison, Lee H

2016-03-18

Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Meningococcal Disease (Bacterial Meningitis) Vaccine and Pregnancy

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Meningococcal Disease (Bacterial Meningitis) Vaccine In every pregnancy, a woman starts out with a 3-5% chance of having a baby with a ... advice from your health care provider. What is meningitis? Meningitis is an infection of the lining around ...

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

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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

Science.gov (United States)

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

Complement pathways and meningococcal disease : diagnostic aspects

DEFF Research Database (Denmark)

Sjöholm, A G; Truedsson, L; Jensenius, Jens Christian

2001-01-01

Complement is an immunological effector system that bridges innate and acquired immunity in several ways. There is a striking association between susceptibility to meningococcal disease and various forms of complement deficiency (1,2). In defense against bacterial infection, the most important fu...

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

OpenAIRE

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 (repr...

[Meningococcal disease: frequently asked questions].

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Cofré, José

2012-12-01

On account of an increase of serogroup W135 meningococcal disease (M.D.) observed in Santiago, Chile, during last two years the medical community has experienced an avidity to update their knowledge about M.D. treatment and its prevention. In a queries and answers mode, the following topics on M.D. are presented: nasopharyngeal carriage and its importance, immunity and protection against the disease, reasons to choice ceftriaxone as the first line antibiotic in treatment, rationality and indications of chemoprophylaxis, fundamentals and advantages of conjugate vaccines, its indications, schedules, contraindications and decisions making in public health.

Meningococcal disease and future drug targets

DEFF Research Database (Denmark)

Gammelgaard, L K; Colding, H; Hartzen, S H

2011-01-01

recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how host immune responses ultimately may aggravate neuropathology and the clinical prognosis. Within this context, particular importance is paid to the endotoxic components that provide potential drug targets...... for novel neuroprotective adjuvants, which are needed in order to improve the clinical management of meningoencephalitis and patient prognosis....

Does Dexamethasone Helps in Meningococcal Sepsis?

OpenAIRE

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 cl...

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

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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.

An evaluation of emerging vaccines for childhood meningococcal disease

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Nelson Christopher B

2011-04-01

Full Text Available Abstract Background Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%. Deliverability

Pros and cons of vaccination against serogroup B meningococcal disease.

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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.

Impact of an Immunization Campaign to Control an Increased Incidence of Serogroup B Meningococcal Disease in One Region of Quebec, Canada.

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De Wals, Philippe; Deceuninck, Geneviève; Lefebvre, Brigitte; Tsang, Raymond; Law, Dennis; De Serres, Gaston; Gilca, Vladimir; Gilca, Rodica; Boulianne, Nicole

2017-05-01

Invasive meningococcal disease (IMD) incidence increased in Quebec, starting in 2003, and was caused by a serogroup B sequence type 269 clone. The Saguenay-Lac-Saint-Jean (SLSJ) region was particularly affected with a rate of 3.4 per 100000 person-years in 2006-2013. In May 2014, an immunization campaign was launched in SLSJ, using the 4-component protein-based meningococcal vaccine (MenB-4C). We aimed to evaluate the impact of the campaign 2 years after its initiation. Immunization registry data and serogroup B invasive meningococcal disease (B-IMD) cases notified to public health authorities and confirmed by culture or polymerase chain reaction from July 1996 to December 2016 were analyzed, including a multivariate Poisson regression model of incidence rates. By the end of the campaign, 82% of the 59000 targeted SLSJ residents between 2 months and 20 years of age had been immunized. Following the initiation of the campaign, no B-IMD case occurred among vaccinees, whereas 2 cases were reported among unvaccinated adult SLSJ residents, and a third case in an unvaccinated child who had stayed in the region during the week prior to disease onset, in 2015. B-IMD incidence decreased in all other regions in the years 2015-2016 but sporadic cases continued to occur. A multivariate analysis showed a significant effect of the campaign in the SLSJ region (relative B-IMD risk: 0.22; P = .04). Results suggest a high level of protection provided by MenB-4C following mass vaccination at regional level. This, along with reassuring safety data, supports the current recommendations for MenB-4C use for controlling outbreaks caused by clones covered by the vaccine. © The Author 2017. 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: Information for Teens and College Students

Science.gov (United States)

... booster. Unvaccinated or incompletely vaccinated first-year college students living in residence halls should receive 1 dose of MCV4. Teens who are unvaccinated or incompletely vaccinated may need to receive an MCV4 if they travel to areas with high rates of meningococcal disease, ...

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias

Directory of Open Access Journals (Sweden)

Matute-Cruz Petra

2009-04-01

Full Text Available Abstract Background Mortality from invasive meningococcal disease (IMD has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods A retrospective analysis was made of clinical reports of all patients (n = 848 diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results Data were recorded on 848 patients, 49 (5.72% of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93. Conclusion Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

New versus old meningococcal group B vaccines: how the new ones may benefit infants & toddlers.

Science.gov (United States)

Panatto, D; Amicizia, D; Lai, P L; Cristina, M L; Domnich, A; Gasparini, R

2013-12-01

Invasive disease caused by Neisseria meningitidis is associated with high mortality and high disability rates and mainly affects children under one year of age. Vaccination is the best way to prevent meningococcal disease, especially in infants and toddlers. The introduction of massive meningococcal serogroup C vaccination has drastically reduced the incidence of disease caused by this serogroup, and serogroup B has now become the main causative agent in several industrialized countries. The first serogroup B vaccines, which were used for more than two decades, were based on outer membrane vesicles and proved to be protective only against specific epidemic strains in Cuba, Norway, Brazil and New Zealand. Moreover, these often elicited a scant immune response in young children. Innovative genomics-based reverse vaccinology subsequently enabled researchers to identify genes encoding for surface proteins that are able to elicit a strong immune response against several B strains. This important discovery led to the development and recent approval in Europe of the four-component meningococcal serogroup B (4CMenB) vaccine. Large clinical trials have shown high immunogenicity and tolerability and acceptable safety levels of 4CMenB in infants and toddlers. This vaccine is expected to cover a large number of circulating invasive strains and may also be efficacious against other serogroups. Young children are particularly vulnerable to the devastating consequences of meningococcal disease. Given the high performance of 4CMenB and its non-interference with routine vaccinations, this age-group will be the first to benefit from the introduction of this vaccine.

Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis.

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Jennifer M Bell

Full Text Available Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92 for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9. Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94 per correctly treated patient.Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost

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

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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 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.

Pre-admission antibiotics for suspected cases of meningococcal disease.

Science.gov (United States)

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 B vaccine. An immunogenic vaccine possibly useful during outbreaks.

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2014-09-01

Invasive meningococcal infections can be life-threatening and cause severe sequelae. Antibiotic therapy is only partially effective. Bexsero is the first meningococcal B vaccine to be approved in the European Union. It contains four capsular antigens from various strains of group B meningococci. Clinical trials of this meningococcal B vaccine did not assess clinical protection. Two immunogenicity studies in adults, one in adolescents and six in infants, are available. They established the immunogenicity of the meningococcal B vaccine, determined age-appropriate vaccination schedules, and verified that concomitant administration of other vaccines did not undermine its immunogenicity. In the absence of relevant clinical trials, an in vitro study showed that sera from vaccinated individuals were likely to have bactericidal activity against 85% of 200 invasive meningococcal B strains isolated in France in 2007-2008. The meningococcal B vaccine provoked local adverse effects in most vaccinees, including local erythema, induration and pain. Fever occurred in about half of vaccinated children. Six cases of Kawasaki syndrome have been reported in children who received the vaccine, compared to only one case in control groups. In practice, the harm-benefit balance of this meningococcal B vaccine justify using it during outbreaks, provided the outbreak strain is covered by the vaccine antigens. Vaccinees should be enrolled in studies designed to evaluate clinical efficacy and to better determine the risk of Kawasaki syndrome.

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

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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.

New recombinant vaccines for the prevention of meningococcal B disease

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Taha MK

2012-06-01

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

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

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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.

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

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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.

Increase of Neisseria meningitidis W:cc11 invasive disease in Chile has no correlation with carriage in adolescents.

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Paulina S Rubilar

Full Text Available Neisseria meningitidis is a human exclusive pathogen that can lead to invasive meningococcal disease or may be carried in the upper respiratory tract without symptoms. The relationship between carriage and disease remains poorly understood but it is widely accepted that decreasing carriage by immunization should lead to a reduction of invasive cases. Latin America has experienced an increased incidence of serogroup W invasive cases of Neisseria meningitidis in the last decade. Specifically in Chile, despite low total incidence of invasive cases, serogroup W has become predominant since 2011 and has been associated with elevated mortality. Expecting to gain insight into the epidemiology of this disease, this study has used molecular typing schemes to compare Neisseria meningitidis isolates causing invasive disease with those isolates collected from adolescent carriers during the same period in Chile. A lower carriage of the serogroup W clonal complex ST-11/ET37 than expected was found; whereas, the same clonal complex accounted for 66% of total invasive meningococcal disease cases in the country that year. A high diversity of PorA variable regions and fHbp peptides was also ascertained in the carrier isolates compared to the invasive ones. According to the results shown here, the elevated number of serogroup W invasive cases in our country cannot be explained by a rise of carriage of pathogenic isolates. Overall, this study supports the idea that some strains, as W:cc11 found in Chile, possess an enhanced virulence to invade the host. Notwithstanding hypervirulence, this strain has not caused an epidemic in Chile. Finally, as genetic transfer occurs often, close surveillance of Neisseria meningitidis strains causing disease, and particularly hypervirulent W:cc11, should be kept as a priority in our country, in order to prepare the best response to face genetic changes that could lead to enhanced fitness of this pathogen.

Systemic meningococcal disease in children: survival analysis, Arkhangelsk region, Northwest Russia, 1991–2011

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O. V. Samodova

2012-01-01

Full Text Available Systemic meningococcal infection requires prompt and adequate medical care. It is considered as unpredictable disease due to extreme severity of a patient’s condition and high risk for fatal outcome. Survival of the children with systemic meningococcal infection was studied. Retrospective cohort includes all cases of systemic meningococcal disease in children arose in Arkhangelsk region in 1991–2011. Rate of fatal outcomes was high (41%. All death cases occurred during first three days of illness. Survival of the patient with correct pre-admission diagnosis was higher in comparison with initially undiagnosed cases. Survival functions were influenced by form of the disease and presence of septic shock. The usage of intramuscular injection of glucocorticoids on pre-admission stage according to the common recommendations did not improve the outcome.

Meningococcal group B vaccines.

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Findlow, Jamie

2013-06-01

Meningococcal disease remains a devastating and feared infection with a significant morbidity and mortality profile. The successful impact of meningococcal capsular group C glyconconjugate vaccines introduced into the UK infant immunization schedule in 1999, has resulted in >80% of disease now being attributable to meningococcal capsular group B (MenB). MenB glyconconjugate vaccines are not immunogenic and hence, vaccine design has focused on sub-capsular antigens. Recently, a four component vaccine to combat MenB disease (4CMenB) has progressed through clinical development and was approved by the European Medicines Agency at the end of 2012. This vaccine has proven safe and immunogenic and has been predicted to provide protection against ~73% of the MenB disease from England and Wales. Recommendation/implementation of the vaccine into the UK infant schedule is currently being evaluated. 4CMenB has the potential to provide protection against a significant proportion of MenB disease in the UK which is currently unpreventable.

Travelers' Health: Meningococcal Disease

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... Zika Travel Information World Map of Zika Country Classification Technical Guidance Risk of Zika Virus at Your ... Meningococcal meningitis is characterized by sudden onset of headache, fever, and stiffness of the neck, sometimes accompanied ...

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

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

2009-01-01

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

Risk factors for meningococcal disease in Cape Town | Moodley ...

African Journals Online (AJOL)

Objective. To determine the risk factors associated with meningococcal disease among children living in Cape Town. Design. A case-control study was conducted from October 1993 to January 1995. Setting. The study population consisted of all children tmder the age of 14 years who were resident in the Cape Town ...

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

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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, PFc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

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.

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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

Meningococcal Disease: Diagnosis and Treatment

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... of limb(s), deafness, nervous system problems, or brain damage. Top of Page Related Links Meningococcal Vaccination Preteen Vaccine Campaign Podcast: Meningitis Immunization for Adolescents Meningitis Sepsis ...

Outbreak of meningococcal disease caused by PorA-deficient meningococci

NARCIS (Netherlands)

van der Ende, A.; Hopman, C. T. P.; Keijzers, W. C. M.; Spanjaard, L.; Lodder, E. B.; van Keulen, P. H. J.; Dankert, J.

2003-01-01

An outbreak of 7 cases of group C meningococcal disease occurred during the last week of July and the first week of August 2001 in the southwestern part of The Netherlands. Characterization of the 7 patients' isolates by various typing methods showed that the isolates were identical, except for the

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

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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

Atypical meningococcal meningitis with rashless presentation：A case report

Institute of Scientific and Technical Information of China (English)

Sunita; Singh Manpreet; Kapoor Dheeraj

2012-01-01

Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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Jacqueline M. Miller

2011-01-01

Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

2011-01-01

Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

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

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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.

Bivalent rLP2086 Vaccine (Trumenba(®)): A Review in Active Immunization Against Invasive Meningococcal Group B Disease in Individuals Aged 10-25 Years.

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Shirley, Matt; Dhillon, Sohita

2015-10-01

Bivalent rLP2086 vaccine (Trumenba(®)) [hereafter referred to as rLP2086] is a Neisseria meningitidis serogroup B (MenB) vaccine recently licensed in the USA for active immunization to prevent invasive disease caused by MenB in individuals 10-25 years of age. rLP2086, which contains two variants of the meningococcal surface protein factor H-binding protein (fHBP), was approved by the FDA under the accelerated approval pathway after the immunogenicity of the vaccine was demonstrated in several phase II trials. This article reviews the immunogenicity and reactogenicity of rLP2086 as demonstrated in the trials with a focus on the US setting and on use of the vaccine as per FDA-approved labeling. rLP2086 is approved in the USA as a three-dose series administered in a 0-, 2-, and 6-month schedule. In the phase II trials, rLP2086 elicited a robust immune response against a panel of MenB test strains. A strong immune response was evident in a marked proportion of subjects after two vaccine doses, with a further increase after a third dose. The four primary test strains used were selected to be representative of MenB strains prevalent in the USA, with each expressing an fHBP variant heterologous to the vaccine antigens. rLP2086 was generally well tolerated in the trials, with most adverse reactions being mild to moderate in severity. Although some questions remain, including the duration of the protective response, rLP2086 vaccine has the potential to be a valuable tool for the prevention of invasive MenB disease.

The capsular group B meningococcal vaccine, 4CMenB : clinical experience and potential efficacy.

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Rollier, Christine S; Dold, Christina; Marsay, Leanne; Sadarangani, Manish; Pollard, Andrew J

2015-01-01

Capsular group B meningococcal disease is a leading cause of childhood meningitis and septicaemia. Up to 10% of sufferers die, and sequelae remain in > 30% of survivors. A vaccine, four component meningococcal group B ( 4CMenB ), designed with the aim to induce broad coverage against this highly variable bacterium, has been licensed in countries including in the European Union, Canada and Australia. Immunogenicity and safety data, published in peer-reviewed literature between 2004 and 2014, are presented in the context of the recent recommendation for the use of the vaccine in infants in the UK. 4CMenB induces significant reactogenicity when administered with routine infant vaccines, in particular with respect to fever rates. Fevers can be somewhat reduced using paracetamol. The efficacy of the vaccine is unknown but has been extrapolated from effectiveness data obtained from use of one of its components in New Zealand, immunogenicity data from clinical trials and estimation of coverage from in vitro studies. These data suggest that the vaccine will prevent a proportion of invasive meningococcal disease cases in infants and young children. Implementation and well-planned post-marketing surveillance will address uncertainties over field effectiveness.

Carriage of Neisseria Species in Communities with Different Rates of Meningococcal Disease

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Nicole Le Saux

1992-01-01

Full Text Available A single clone, Neisseria meningitidis serogroup C (C:2a:P1.2, was isolated from seven patients during a cluster of cases of meningococcal disease in Ontario in 1989. To determine whether the clone was present in asymptomatic individuals in the same population, pharyngeal swabs were taken from 7% (644 of 9125 of residents who were vaccinated during the outbreak. Rates of isolation of Neisseria species were also compared to those in two other geographical areas which did not have an elevated incidence of meningococcal disease. The rate of carriage of N meningitidis in the asymptomatic individuals sampled was between 1.9% and 5.4%. The clone isolated from patients was not present among the carrier strains as determined by sero- and subtyping and electrophoretic analysis of metabolic enzymes. Age greater than six years was the only factor associated with colonization with N meningitidis.

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

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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.…

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.

Science.gov (United States)

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.

Meningococcal serogroup B strain coverage of the multicomponent 4CMenB vaccine with corresponding regional distribution and clinical characteristics in England, Wales, and Northern Ireland, 2007-08 and 2014-15: a qualitative and quantitative assessment.

Science.gov (United States)

Parikh, Sydel R; Newbold, Lynne; Slater, Stephanie; Stella, Maria; Moschioni, Monica; Lucidarme, Jay; De Paola, Rosita; Giuliani, Maria; Serino, Laura; Gray, Stephen J; Clark, Stephen A; Findlow, Jamie; Pizza, Mariagrazia; Ramsay, Mary E; Ladhani, Shamez N; Borrow, Ray

2017-07-01

The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes. Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases. In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease. In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes. Public Health England, GlaxoSmithKline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis

NARCIS (Netherlands)

Brouwer, Matthijs C.; Read, Robert C.; van de Beek, Diederik

2010-01-01

Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal disease. We systematically reviewed the published work for case control studies on the influence of host genetics on severity and

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

Science.gov (United States)

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.

Effectiveness of antibiotics given before admission in reducing mortality from meningococcal disease: systematic review.

NARCIS (Netherlands)

Hahné, Susan J M; Charlett, André; Purcell, Bernadette; Samuelsson, Susanne; Camaroni, Ivonne; Ehrhard, Ingrid; Heuberger, Sigrid; Santamaria, Maria; Stuart, James M

2006-01-01

OBJECTIVE: To review the evidence for effectiveness of treatment with antibiotics before admission in reducing case fatality from meningococcal disease. DESIGN: Systematic review. DATA SOURCES: Cochrane register of trials and systematic reviews, database of abstracts of reviews of effectiveness,

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

Science.gov (United States)

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

2013-05-28

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. 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. 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. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Meningitis - meningococcal

Science.gov (United States)

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

Meningococcal disease in children in Merseyside, England: a 31 year descriptive study.

Directory of Open Access Journals (Sweden)

Michelle C Stanton

Full Text Available Meningococcal disease (MCD is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM, septicaemia (MS, or as a combination of the two syndromes (MM/MS. We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157. Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM and serogroup C disease (compared to serogroup B were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08 and 2.18 (95% CI 1.26 to 3.80 respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41 than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD.

Meningococcal disease, a clinical and epidemiological review.

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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.

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

Science.gov (United States)

... 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 ...

Meningococcal Immunizations for Preteens and Teens

Centers for Disease Control (CDC) Podcasts

2015-08-11

This podcast provides information about vaccine recommendations to help prevent meningococcal disease in preteens and teens.  Created: 8/11/2015 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Bacterial Diseases (DBD), Meningitis and Vaccine Preventable Diseases Branch (MVPDB).   Date Released: 8/11/2015.

A large portion of meningococcal antigen typing system-negative meningococcal strains from spain is killed by sera from adolescents and infants immunized with 4CMenB.

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Abad, R; Biolchi, A; Moschioni, M; Giuliani, M M; Pizza, M; Vázquez, J A

2015-04-01

A new vaccine (the 4CMenB 4-component protein vaccine [Bexsero], which includes PorA, factor H-binding protein [fHbp], neisserial heparin-binding antigen [NHBA], and Neisseria adhesin A [NadA]) against serogroup B meningococci has recently been approved for use in people older than age 2 months in Europe, Australia, and Canada. Preapproval clinical efficacy studies are not feasible for invasive meningococcal disease because its incidence is low/very low, and the serum bactericidal antibody (SBA) titer (or the human SBA [hSBA] titer when human complement is used in the assay) has been used as a surrogate marker of protection. However, the hSBA assay cannot be used on a large scale, and therefore, a meningococcal antigen typing system (MATS) was developed. MATS combines conventional PorA genotyping with an enzyme-linked immunosorbent assay (ELISA) that quantifies both the expression and the cross-reactivity of antigenic variants. The assay has been used to evaluate the potential of the 4CMenB meningococcal group B vaccine to cover group B strains in several countries. Some recent data suggest that MATS is a conservative predictor of strain coverage. We used pooled sera from adolescents and infants to test by the hSBA assay 10 meningococcal group B strains isolated in Spain that were negative for the 3 antigens (n = 9) or that had very low levels of the 3 antigens (n = 1) by MATS. We found that all strains were killed by sera from adolescents and that 5 of the 10 strains were also killed, although at a low titer, by sera from infants. Our data confirm that MATS underestimates vaccine coverage. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Meningococcal meningitis C in Tamil Nadu, public health perspectives.

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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.

The changing epidemiology of meningococcal disease in Quebec, Canada, 1991-2011: potential implications of emergence of new strains.

Directory of Open Access Journals (Sweden)

Rodica Gilca

Full Text Available BACKGROUND: In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination. METHODOLOGY: IMD cases reported to the provincial notifiable disease registry in 1991-2011 and isolates submitted for laboratory surveillance in 1997-2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST by using multilocus sequence typing (MLST were performed. RESULTS: Yearly overall IMD incidence rates ranged from 2.2-2.3/100,000 in 1991-1992 to 0.49/100,000 in 1999-2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997-2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups. CONCLUSION: Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in

Potential Capsule Switching from Serogroup Y to B: The Characterization of Three such Neisseria meningitidis Isolates Causing Invasive Meningococcal Disease in Canada

Directory of Open Access Journals (Sweden)

Raymond SW Tsang

2005-01-01

Full Text Available Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

NNDSS - Table II. Meningococcal to Pertussis

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal to Pertussis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

Meningococcal Vaccine (For Parents)

Science.gov (United States)

... previous dose of meningococcal vaccine, to the DTaP vaccine , or to latex If your child has a history of Guillain-Barré syndrome (a disease of the nervous system that causes progressive weakness), talk to your doctor about whether the vaccines are a good idea. Caring for Your Child ...

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero(®) to reduce meningococcal group B disease in Germany.

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Christensen, Hannah; Irving, Tom; Koch, Judith; Trotter, Caroline L; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hellenbrand, Wiebke

2016-06-17

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute

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

Directory of Open Access Journals (Sweden)

Thomas E Delea

Full Text Available 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.

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

Science.gov (United States)

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.

Primary Meningococcal Polyarthritis in an Adult Woman

Directory of Open Access Journals (Sweden)

José Celso Giordan Cavalcanti Sarinho

2015-01-01

Full Text Available Primary joint infection caused by the Gram-negative bacteria Neisseria meningitidis is rare. Normally, joint involvement comes secondary to meningitis or severe sepsis caused by this agent. When primary arthritis is seen, monoarthritis is the most common presentation. A meningococcal polyarthritis is described in less than 10 case reports according to current literature. This case report aims to briefly review this rare clinical event in an adult woman with no previous history of rheumatological disease. Early diagnosis of polyarthritis caused by meningococcal bacteria usually present a good prognosis when properly treated.

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

Science.gov (United States)

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▿

Science.gov (United States)

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

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

Science.gov (United States)

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

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.

Temporal associations between national outbreaks of meningococcal serogroup W and C disease in the Netherlands and England: an observational cohort study.

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Knol, Mirjam J; Hahné, Susan J M; Lucidarme, Jay; Campbell, Helen; de Melker, Hester E; Gray, Stephen J; Borrow, Ray; Ladhani, Shamez N; Ramsay, Mary E; van der Ende, Arie

2017-10-01

Since 2009, the incidence of meningococcal serogroup W disease has increased rapidly in the UK because of a single strain (the so-called original UK strain) belonging to the hypervirulent sequence type-11 clonal complex (cc11), with a variant outbreak strain (the so-called 2013 strain) emerging in 2013. Subsequently, the Netherlands has had an increase in the incidence of meningococcal serogroup W disease. We assessed the temporal and phylogenetic associations between the serogroup W outbreaks in the Netherlands and England, and the historical serogroup C outbreaks in both countries. For this observational cohort study, we used national surveillance data for meningococcal serogroup W and serogroup C disease in the Netherlands and England for the epidemiological years (July to June) 1992-93 to 2015-16. We also did whole genome sequencing and core genome multilocus sequence typing (1546 loci) on serogroup W disease isolates from both countries for surveillance years 2008-09 to 2015-16. We used Poisson regression to compare the annual relative increase in the incidence of serogroup W and serogroup C between both countries. In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015-16 compared with 2014-15, with an incidence rate ratio of 5·2 (95% CI 2·0-13·5) and 11% case fatality. In England, the incidence increased substantially in 2012-13 compared with 2011-12, with an incidence rate ratio of 1·8 (1·2-2·8). The relative increase in the Netherlands from 2014-15 to 2015-16 was 418% (95% CI 99-1248), which was significantly higher than the annual relative increase of 79% (61-99) per year in England from 2011-12 to 2014-15 (p=0·03). Cases due to meningococcal serogroup W cc11 (MenW:cc11) emerged in 2012-13 in the Netherlands. Of 29 MenW:cc11 cases found up to 2015-16, 26 (90%) were caused by the 2013 strain. For both the current serogroup W outbreak and the historical serogroup C outbreak, the increase in incidence

Risk of transmitting meningococcal infection by transient contact on aircraft and other transport.

Science.gov (United States)

Rachael, T; Schubert, K; Hellenbrand, W; Krause, G; Stuart, J M

2009-08-01

Contact tracing of persons with meningococcal disease who have travelled on aeroplane or other multi-passenger transport is not consistent between countries. We searched the literature for clusters of meningococcal disease linked by transient contact on the same plane, train, bus or boat. We found reports of two clusters in children on the same school bus and one in passengers on the same plane. Cases within each of these three clusters were due to strains that were genetically indistinguishable. In the aeroplane cluster the only link between the two cases was through a single travel episode. The onset of illness (2 and 5 days after the flight) is consistent with infection from an unidentified carrier around the time of air travel. In contrast to the established risk of transmission from a case of tuberculosis, it is likely that the risk from a case of meningococcal disease to someone who is not identified as a close contact is exceedingly low. This should be considered in making international recommendations for passenger contact tracing after a case of meningococcal disease on a plane or other multi-passenger transport.

Meningococcal vaccination for international travellers from Greece visiting developing countries.

Science.gov (United States)

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 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.

Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero(®)).

Science.gov (United States)

Ladhani, Shamez N; Cordery, Rebecca; Mandal, Sema; Christensen, Hannah; Campbell, Helen; Borrow, Ray; Ramsay, Mary E

2014-11-01

To assess the potential use of a protein-based meningococcal group B (MenB) vaccine (Bexsero(®)) in addition to antibiotic chemoprophylaxis for preventing secondary cases. Published studies on the risk of secondary meningococcal infections were used to estimate the numbers needed to vaccinate (NNV) with Bexsero(®) to prevent a secondary case in household and educational settings. Most secondary cases occur within a few days of diagnosis in the index case. Unlike conjugate vaccines, early protection offered after a single dose of Bexsero(®) is likely to be low, particularly in young children, who are at higher risk of secondary infection. NNV was dependent on predicted meningococcal strain coverage, estimated onset of protection after one Bexsero(®) dose and estimated vaccine efficacy. Even in the most favourable scenario where we assume the vaccine is administered within 4 days of the index case and prevents 90% of cases occurring after 14 days, the NNV for household contacts was >1000. NNV in educational settings was much higher. The estimated NNV should be taken into account when deciding policy to recommend Bexsero(®) for close contacts of single cases in household or educational settings. Bexsero(®) may have a protective role in clusters and outbreaks. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: A prospective, observational cohort study

NARCIS (Netherlands)

J.J. Verhoeven (Jennifer)

2011-01-01

textabstractIntroduction: The objective of this study was to investigate the occurrence of hyperglycemia and insulin response in critically ill children with meningococcal disease in the intensive care unit of an academic children's hospital.Methods: Seventy-eight children with meningococcal disease

Association of meningococcal serotypes with the course of disease: serotypes 2a and 2b in the Netherlands, 1959-1981

NARCIS (Netherlands)

Spanjaard, L.; Bol, P.; de Marie, S.; Zanen, H. C.

1987-01-01

Case histories of 692 patients with meningococcal disease due to serogroup B, C, or W (W-135) were reviewed to study the association of the serotypes 2a and 2b with the course of disease. The case-fatality rate in group B disease was significantly associated with serotype 2b (B:2b) strains (P =

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

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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.

Serogroup B Meningococcal Vaccine (MenB)

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What are meningococcal group B vaccines?Two serogroup B meningococcal group B vaccines (Bexsero and Trumenba) have been licensed by the Food and Drug ... Who should not get meningococcal group B vaccine or should wait?Tell the person ... you the vaccine:If you have any severe, life-threatening allergies. ...

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

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

2016-01-01

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

Influence of antibiotic therapy prior to admission on the efficacy of classical methods for the diagnosis of meningococcal disease.

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

2014-01-01

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

Effects of meteorological factors on the incidence of meningococcal ...

African Journals Online (AJOL)

Background and Objectives: Substantial climate changes have led to the emergence and re-emergence of various infectious diseases worldwide, presenting an imperative need to explore the effects of meteorological factors on serious contagious disease incidences such as that of meningococcal meningitis (MCM).

Meningococcal Vaccines: What You Need to Know

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... Español Text Size Email Print Share Meningococcal ACWY Vaccines: What You Need to Know (VIS) Page Content ... to help protect against serogroup B . Meningococcal ACWY Vaccines There are two kinds of meningococcal vaccines licensed ...

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

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Petousis-Harris, Helen

2017-10-19

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

A Rare Case of Primary Meningococcal Myopericarditis in a 71-Year-Old Male

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Odilia I. Woudstra

2016-01-01

Full Text Available We describe a case of primary meningococcal C pericarditis with myocardial involvement in a 71-year-old male that is thus far the oldest patient with isolated meningococcal pericardial disease and only the third patient with primary meningococcal myopericarditis described in English literature. Our patient was successfully treated by full sternotomy and surgical drainage combined with intravenous ceftriaxone. Mild symptoms unresponsive to anti-inflammatory treatment and leukocytosis may guide clinicians towards the correct diagnosis. It is important to recognize this cause of pericarditis as the relatively mild clinical presentation may rapidly progress into tamponade and right-sided heart failure.

Enter B and W: two new meningococcal vaccine programmes launched

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Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J

2016-01-01

In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a gr...

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

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

2014-12-01

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

Vaccine Preventability of Meningococcal Clone, Greater Aachen Region, Germany

NARCIS (Netherlands)

Elias, Johannes; Schouls, Leo M.; van de Pol, Ingrid; Keijzers, Wendy C.; Martin, Diana R.; Glennie, Anne; Oster, Philipp; Frosch, Matthias; Vogel, Ulrich; van der Ende, Arie

2010-01-01

Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city

The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

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Lisa A Lewis

2010-07-01

Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines

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Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System

2013-01-01

We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166

[Meningococcal C conjugate vaccine: Impact of a vaccination program and long-term effectiveness in Navarra, Spain, 2000-2014].

Science.gov (United States)

Morales, Desirée; García-Cenoz, Manuel; Moreno, Laura; Bernaola, Enrique; Barricarte, Aurelio; Castilla, Jesús

2016-12-01

Since 2000, when the meningococcal serogroupC conjugate vaccine (MenCC) was introduced in the childhood immunization schedule in Spain, several changes in the schedule and catch-up campaigns have been performed. We aim to estimate the impact and effectiveness of this vaccine in Navarra up to 2014. The impact of the vaccination program was analysed by comparing incidence, mortality and lethality rates of disease before (1995-1999) and after (2004-2014) the introduction of the MenCC. Vaccine effectiveness was estimated using the screening method (Farrington) and the indirect cohort method (Broome). Data on cases were obtained from the active surveillance of meningococcal disease. During 1995-1999 the mean annual incidence of meningococcalC disease was 1.32 per 100,000, and 7.18 per 100,000 in children younger than 15years. The fall of meningococcalC disease incidence was significant in cohorts targeted for vaccination from the beginning and progressive in the general population. No cases were reported between 2011 and 2014. The estimated vaccine effectiveness was 96% by the screening method, and 99% by the indirect cohort method. The MenCC vaccination program has been successful in decreasing the incidence rate of serogroupC meningococcal disease in Navarra, and schedule changes have maintained high vaccine effectiveness throughout the study period. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

A Seroepidemiological Study of Serogroup A Meningococcal Infection in the African Meningitis Belt.

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Olivier Manigart

Full Text Available The pattern of epidemic meningococcal disease in the African meningitis belt may be influenced by the background level of population immunity but this has been measured infrequently. A standardised enzyme-linked immunosorbent assay (ELISA for measuring meningococcal serogroup A IgG antibodies was established at five centres within the meningitis belt. Antibody concentrations were then measured in 3930 individuals stratified by age and residence from six countries. Seroprevalence by age was used in a catalytic model to determine the force of infection. Meningococcal serogroup A IgG antibody concentrations were high in each country but showed heterogeneity across the meningitis belt. The geometric mean concentration (GMC was highest in Ghana (9.09 μg/mL [95% CI 8.29, 9.97] and lowest in Ethiopia (1.43 μg/mL [95% CI 1.31, 1.57] on the margins of the belt. The force of infection was lowest in Ethiopia (λ = 0.028. Variables associated with a concentration above the putative protective level of 2 μg/mL were age, urban residence and a history of recent vaccination with a meningococcal vaccine. Prior to vaccination with the serogroup A meningococcal conjugate vaccine, meningococcal serogroup A IgG antibody concentrations were high across the African meningitis belt and yet the region remained susceptible to epidemics.

Enter B and W: two new meningococcal vaccine programmes launched.

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Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J

2016-01-01

In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone of N. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2. 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/

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

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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/

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage.

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Frosi, Giacomo; Biolchi, Alessia; Lo Sapio, Morena; Rigat, Fabio; Gilchrist, Stefanie; Lucidarme, Jay; Findlow, Jamie; Borrow, Ray; Pizza, Mariagrazia; Giuliani, Marzia Monica; Medini, Duccio

2013-10-09

4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology. To experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting. We used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007-2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P=0.022). MATS predicted coverage of 70% (95% CI, 55-85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72-95%). MATS had 78% accuracy and 96% positive predictive value against hSBA. MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis

NARCIS (Netherlands)

Scholten, R. J.; Bijlmer, H. A.; Poolman, J. T.; Kuipers, B.; Caugant, D. A.; van Alphen, L.; Dankert, J.; Valkenburg, H. A.

1993-01-01

In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible

History of meningococcal vaccines and their serological correlates of protection.

Science.gov (United States)

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.

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

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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.

CLINICAL-EPIDEMIOLOGICAL FEATURES AND OUTCOME OF GENERALIZED FORMS OF MENINGOCOCCAL INFECTION IN CHILDREN

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G. P. Martynova

2017-01-01

Full Text Available The objective of the research was to study clinical and epidemiological features and outcomes of generalized forms of meningococcal infection in children from Krasnoyarsk and Krasnoyarsk Territory during the period from 2012 to 2016. Materials and methods. A retrospective analysis of 57 medical records of hospital patients with generalized forms of meningococcal infection was carried out in the infectious and resuscitative departments of the Krasnoyarsk Clinical Hospital No. 1 from 2012 to 2016, including 12 protocols of pathologoanatomical studies of the deceased patients and 45 medical cards of ambulatory patients – convalescents of the disease from 2012 to 2016. Results. The epidemic situation for meningococcal infection in Krasnoyarsk Territory from 2012 to 2016 is characterized by signs of inter-epidemic period. Children of the first 3 years of life are in the group of high risk for the development of GFMI, which accounts for 74% of the total number of cases of children aged 14. There are signs of meningococcal infection «aging» – in the age structure the number of children in the first year of life decreased, while the proportion of children aged 4–7 and 7–14 increased compared to previous decades. There is a tendency to a decrease in the proportion of the combined forms with an increase in the frequency of «pure» meningococcemia. In recent years there has been an «atypical» course of generalized forms of the disease, when classical hemorrhagic necrotic rashes appear only on the 3rd – 4th day of the disease. In convalescents who underwent a combined form of MI and «pure» meningitis severe residual effects leading patients to disability are possible to develop. Conclusion. The use of polyvalent conjugated vaccines in potential risk groups will allow us to reduce the morbidity and mortality from generalized forms of meningococcal infection, including younger children.

Meningococcal carriage in the African meningitis belt

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2013-01-01

A meningococcal serogroup A polysaccharide/tetanus toxoid conjugate vaccine (PsA-TT) (MenAfriVac#x2122;) is being deployed in countries of the African meningitis belt. Experience with other polysaccharide/protein conjugate vaccines has shown that an important part of their success has been their ability to prevent the acquisition of pharyngeal carriage and hence to stop transmission and induce herd immunity. If PsA-TT is to achieve the goal of preventing epidemics, it must be able to prevent the acquisition of pharyngeal carriage as well as invasive meningococcal disease and whether PsA-TT can prevent pharyngeal carriage needs to be determined. To address this issue, a consortium (the African Meningococcal Carriage (MenAfriCar) consortium) was established in 2009 to investigate the pattern of meningococcal carriage in countries of the African meningitis belt prior to and after the introduction of PsA-TT. This article describes how the consortium was established, its objectives and the standardised field and laboratory methods that were used to achieve these objectives. The experience of the MenAfriCar consortium will help in planning future studies on the epidemiology of meningococcal carriage in countries of the African meningitis belt and elsewhere. Un vaccin conjugué contenant un polysaccharide du sérogroupe A méningococcique et une anatoxine du tétanos (PsA-TT) (MenAfriVac™) est en cours de déploiement dans les pays de la ceinture africaine de la méningite. L’ expérience avec d’ autres vaccins conjugués polysaccharide/protéine a montré qu’ une partie importante de leur succès a été leur capacité à empêcher l’ acquisition du portage pharyngé et donc à arrêter la transmission et à induire une immunité de group. Si PsA-TT doit d’ atteindre l’ objectif de prévenir les épidémies, il devrait être en mesure d’ empêcher l’ acquisition du portage pharyngé ainsi que la méningococcie invasive et le fait que PsA-TT puisse emp

Characterization of fHbp, nhba (gna2132), nadA, porA, and sequence type in group B meningococcal case isolates collected in England and Wales during January 2008 and potential coverage of an investigational group B meningococcal vaccine.

Science.gov (United States)

Lucidarme, Jay; Comanducci, Maurizio; Findlow, Jamie; Gray, Stephen J; Kaczmarski, Edward B; Guiver, Malcolm; Vallely, Pamela J; Oster, Philipp; Pizza, Mariagrazia; Bambini, Stefania; Muzzi, Alessandro; Borrow, Ray

2010-06-01

Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (n = 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for fHbp, nhba, and porA were identified in all of the isolates, of which 22% were also found to harbor nadA alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%.

Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives

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Lourdes Almeida-González

2004-10-01

disponibilidad de vacuna y de medicamentos para quimioprofilaxis, debido a que se ha documentado un incremento de casos de enfermedad por N. meningitidis, serogrupo C, en el país. Es por lo anterior que esta revisión está dirigida a proporcionar al personal de salud un recordatorio de los aspectos relevantes de la epidemiología, y de los clínicos y preventivos de la enfermedad meningocóccica.Bacterial meningitis constitutes a significant global public health problem. In particular, Neisseria meningitidis continues to be a public health problem among human populations in both developed and developing countries. Meningococcal infection is present as an endemic and an epidemic disease. Meningococcal disease is manifested not only as meningitis, but also as meningococcemia. The latter is usually fulminant. The global persistence of N. meningitidis is due to the significant number of carriers and the dynamics of transmission and disease. Approximately 500 million people worldwide are carriers of the bacterium in their nasopharynx. Multiple factors have been identified that predispose to the transmissibility of N. meningitidis, including active or passive inhalation tobacco smoking, upper viral respiratory tract infections, drought seasons, and overcrowding. These factors explain the frequent occurrence of outbreaks in military barracks, schools, prisons, and dormitories. Some of the determinants of invasiveness of the bacteria include nasopharyngeal mucosal damage in colonized individuals, virulence of the strains, absence of bactericidal antibodies, and deficiencies of the complement system. During both endemic and epidemic scenarios of meningococcal disease, control measures should include treating the cases with appropriate antimicrobial therapy (penicillin, ceftriaxone, or chloramphenicol; providing chemoprophylactic drugs to contacts (rifampin or ciprofloxacin, and close observation of contacts. Nevertheless, the key to effective control and prevention of meningococcal

MRI evaluation and follow-up of bone necrosis after meningococcal infection and disseminated intravascular coagulation

International Nuclear Information System (INIS)

Damry, N.; Schurmans, T.; Perlmutter, N.

1993-01-01

Disseminated intravascular coagulation (DIC) is a serious complication of meningococcal septicaemia. It often results in infarction of various tissues namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones. We describe a patient who presented bone lesions after meningococcal septicaemia. In addition to plain radiography and scintigraphy the lesions were evaluated with MRI and have proved to be extensive and still progressive, approxximately 18 months after the onset of the disease. (orig.)

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

Science.gov (United States)

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.

Bacterial Meningitis in Brazil: Baseline Epidemiologic Assessment of the Decade Prior to the Introduction of Pneumococcal and Meningococcal Vaccines.

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Luciano Cesar Pontes Azevedo

Full Text Available Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010.All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8% were due to bacterial meningitis (excluding tuberculosis. Of these, 34,997 (31.7% were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000-2002 to 2.14/100,000 in 2009-2010 (p<0.01. Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter.Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil. Furthermore, this study provides a baseline

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents

DEFF Research Database (Denmark)

Vesikari, Timo; Østergaard, Lars Jørgen; Diez-Domingo, Javier

2015-01-01

BACKGROUND: Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years....... Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents. METHODS: Healthy adolescents (11 to ... bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events. RESULTS: Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers...

Strong Public Health Recommendations from Weak Evidence? Lessons Learned in Developing Guidance on the Public Health Management of Meningococcal Disease

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Germaine Hanquet

2015-01-01

Full Text Available The evidence underpinning public health policy is often of low quality, leading to inconsistencies in recommended interventions. One example is the divergence in national policies across Europe for managing contacts of invasive meningococcal disease. Aiming to develop consistent guidance at the European level, a group of experts reviewed the literature and formulated recommendations. The group defined eight priority research questions, searched the literature, and formulated recommendations using GRADE methodology. Five of the research questions are discussed in this paper. After taking into account quality of evidence, benefit, harm, value, preference, burden on patient of the intervention, and resource implications, we made four strong recommendations and five weak recommendations for intervention. Strong recommendations related not only to one question with very low quality of evidence as well as to two questions with moderate to high quality of evidence. The weak recommendations related to two questions with low and very low quality of evidence but also to one question with moderate quality of evidence. GRADE methodology ensures a transparent process and explicit recognition of additional factors that should be considered when making recommendations for policy. This approach can be usefully applied to many areas of public health policy where evidence quality is often low.

Important role for Toll-like receptor 9 in host defense against meningococcal sepsis

DEFF Research Database (Denmark)

Sjölinder, Hong; Mogensen, Trine; Kilian, Mogens

2008-01-01

have been reported to be involved in the host response to N. meningitidis. While TLR4 has been suggested to play an important role in early containment of infection, the roles of TLR2 and TLR9 in meningococcal disease are not well described. Using a model for meningococcal sepsis, we report that TLR9...... and induction of cytokine gene expression were independent of TLR2 or TLR9 in macrophages and conventional dendritic cells. In contrast, plasmacytoid dendritic cells relied entirely on TLR9 to induce these activities. Thus, our data demonstrate an important role for TLR9 in host defense against N. meningitidis....

Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub-Saharan Africa: implications for the susceptibility to meningococcal disease.

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Franco-Jarava, C; Comas, D; Orren, A; Hernández-González, M; Colobran, R

2017-08-01

Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 families, and most C5 mutations (13 of 17) have been found in single families. However, the recently described C5 p.A252T mutation is reported to be associated with approximately 7% of meningococcal disease cases in South Africa. This finding raises the question of whether the mutation may be prevalent in other parts of Africa or other continental regions. The aim of this study was to investigate the prevalence of C5 p.A252T in Africa and other regions and discuss the implications for prophylaxis against meningococcal disease. In total, 2710 samples from healthy donors within various populations worldwide were analysed by quantitative polymerase chain reaction (qPCR) assay to detect the C5 p.A252T mutation. Eleven samples were found to be heterozygous for p.A252T, and nine of these samples were from sub-Saharan African populations (allele frequency 0·94%). Interestingly, two other heterozygous samples were from individuals in populations outside Africa (Israel and Pakistan). These findings, together with data from genomic variation databases, indicate a 0·5-2% prevalence of the C5 p.A252T mutation in heterozygosity in sub-Saharan Africa. Therefore, this mutation may have a relevant role in meningococcal disease susceptibility in this geographical area. © 2017 British Society for Immunology.

Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study.

Science.gov (United States)

Parikh, Sydel R; Andrews, Nick J; Beebeejaun, Kazim; Campbell, Helen; Ribeiro, Sonia; Ward, Charlotte; White, Joanne M; Borrow, Ray; Ramsay, Mary E; Ladhani, Shamez N

2016-12-03

In September, 2015, the UK became the first country to introduce the multicomponent group B meningococcal (MenB) vaccine (4CMenB, Bexsero) into a publicly funded national immunisation programme. A reduced two-dose priming schedule was offered to infants at 2 months and 4 months, alongside an opportunistic catch-up for 3 month and 4 month olds. 4CMenB was predicted to protect against 73-88% of MenB strains. We aimed to assess the effectiveness and impact of 4CMenB in vaccine-eligible infants in England. Public Health England (PHE) undertakes enhanced surveillance of meningococcal disease through a combination of clinical, public health, and laboratory reporting. Laboratory-confirmed cases of meningococcal disease are followed up with PHE local health protection teams, general practitioners, and hospital clinicians to collect demographic data, vaccination history, clinical presentation, and outcome. For cases diagnosed between Sept 1, 2015, and June 30, 2016, vaccine effectiveness was assessed using the screening method. Impact was assessed by comparing numbers of cases of MenB in vaccine-eligible children to equivalent cohorts in the previous 4 years and to cases in vaccine-ineligible children. Coverage of 4CMenB in infants eligible for routine vaccination was high, achieving 95·5% for one dose and 88·6% for two doses by 6 months of age. Two-dose vaccine effectiveness was 82·9% (95% CI 24·1-95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%. Compared with the prevaccine period, there was a 50% incidence rate ratio (IRR) reduction in MenB cases in the vaccine-eligible cohort (37 cases vs average 74 cases; IRR 0·50 [95% CI 0·36-0·71]; p=0·0001), irrespective of the infants' vaccination status or predicted MenB strain coverage. Similar reductions were observed even after adjustment for disease trends in vaccine-eligible and vaccine-ineligible children. The two-dose 4CMen

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

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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

Annual vaccine-preventable disease report for New South Wales, Australia, 2014

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Nathan Saul

2017-06-01

Full Text Available This report provides an epidemiological description of selected vaccine-preventable diseases in New South Wales (NSW, Australia, for 2014 to inform ongoing disease monitoring and control efforts. A trend of increasing pertussis notifications was observed, beginning midway through 2014 with the highest disease rates in the 5–9 year age group. Measles notifications increased to 67 cases in 2014 from 34 cases in 2013. Measles cases were associated with travel-related importations—predominantly from the Philippines—and secondary transmission increased compared to 2013 involving three main disease clusters. Notifications of invasive meningococcal disease continued to decline across the state with meningococcal B remaining the most common serogroup in NSW. Increasing rates of pertussis notifications from mid-2014 may indicate the beginning of an epidemic, ending the period of low transmission observed in 2013 and the first half of 2014. An increase in measles notifications in 2014, including secondary transmission, indicates the continued need for public health actions including robust follow-up and awareness campaigns.

Pharmaceutical Approval Update

OpenAIRE

Gohil, Kunj

2015-01-01

Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis

MenB-FHbp Meningococcal Group B Vaccine (Trumenba®): A Review in Active Immunization in Individuals Aged ≥ 10 Years.

Science.gov (United States)

Shirley, Matt; Taha, Muhamed-Kheir

2018-02-01

MenB-FHbp (bivalent rLP2086; Trumenba ® ) is a recombinant protein-based vaccine targeting Neisseria meningitidis serogroup B (MenB), which has recently been licensed in the EU for active immunization to prevent invasive disease caused by MenB in individuals ≥ 10 years of age. The vaccine, which contains a variant from each of the two identified subfamilies of the meningococcal surface protein factor H-binding protein (fHBP), has been licensed in the USA for active immunization in individuals 10-25 years of age since 2014. This article reviews the immunogenicity, reactogenicity and tolerability of MenB-FHbp, with a focus on the EU label and the European setting. As demonstrated in an extensive program of clinical trials in adolescents and young adults, a two-dose or three-dose series of MenB-FHbp elicits a strong immune response against a range of MenB test strains selected to be representative of strains prevalent in Europe and the USA. Follow-up studies investigating the persistence of the MenB-FHbp immune response and the effect of a booster dose of the vaccine indicate that a booster dose should be considered (following a primary vaccine series) in individuals at continued risk of invasive meningococcal disease. MenB-FHbp vaccine appears to be moderately reactogenic but, overall, is generally well tolerated, with most adverse reactions being mild to moderate in severity. Although post-marketing, population-based data will be required to establish the true effectiveness of the vaccine, currently available data indicate that MenB-FHbp, in a two-dose or three-dose series, is likely to provide broad protection against MenB strains circulating in Europe.

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

Science.gov (United States)

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.

Vaccines against invasive Salmonella disease

Science.gov (United States)

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

[Vaccinal strategies in response to new epidemiological challenges in 2010. Reasonable hope for a "B" meningococcal vaccine].

Science.gov (United States)

Nicolas, P

2010-08-01

In 2010, vaccines have achieved good effectiveness against invasive meningococcal infection. Development of monovalent and bivalent polysaccharide (PS) vaccines in the 70s and later of tetravalent PS vaccine (ACWY) was followed by development in 2003 of a trivalent ACW vaccine in response to the W135 or mixed A/W135 epidemics that appeared in Africa. More recently PS-conjugated vaccines have shown numerous advantages in comparison with PS vaccines. Mass vaccination campaigns with the C-conjugated vaccine have almost completely eradicated group C meningitis in the UK. It is hoped that introduction of the A-conjugated vaccine MenAfriVac in Africa at the end of year 2010 will end group A meningococcal epidemics in the meningitis belt. The problem of group B meningococcal meningitis has not been completely resolved. For the B strain that has been implicated in hyperendemic waves, a protein vaccine has been produced from outer membrane vesicles (OMV). Use of OMV vaccines achieved good results in Norway and recently in New Zealand. The Norwegian vaccine was also used in Normandy since the strain responsible for the Norman epidemic showed the same PorA as the Norwegian strain. In this regard, a major limitation for OMV vaccines is that they are effective only against the immuno-dominant porin A protein. Current efforts to develop a vaccine against group B meningococci causing sporadic cases are promising. Research is being focused on a blend of surface proteins targeting most of circulating isolates. Field tests will be carried out in the next years, but it is probable that the efficacy of these vaccines will be short-lived since meningococcal antigens vary over time.

A Case of High Mortality, Treated with Multidisciplinary Approach in Intensive Care: Meningococcal Meningitis

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Mehtap Pehlivanlar Küçük

2018-04-01

Full Text Available Meningococcemia is a highly mortal disease that can cause septic shock and multiple organ failure, which can be accompanied by sudden onset, rapid course, purpura fulminans and diffuse intravenous coagulation tables. Mortality increases when meningococcal causes to meningitis. The fact that it is the cause of neurological sequelae and extremity losses even in the recovering cases makes the support provided by the intensive care unit quite important in the management of cases. A case with meningococcal meningitis with high mortality, who was successfully treated through the use of supportive methods, such as monitorization, mechanical ventilation practices with new modalities, plasmapheresis and sympathetic ganglion blockage, has been presented in company with the literature.

Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial.

Science.gov (United States)

Read, Robert C; Baxter, David; Chadwick, David R; Faust, Saul N; Finn, Adam; Gordon, Stephen B; Heath, Paul T; Lewis, David J M; Pollard, Andrew J; Turner, David P J; Bazaz, Rohit; Ganguli, Amitava; Havelock, Tom; Neal, Keith R; Okike, Ifeanyichukwu O; Morales-Aza, Begonia; Patel, Kamlesh; Snape, Matthew D; Williams, John; Gilchrist, Stefanie; Gray, Steve J; Maiden, Martin C J; Toneatto, Daniela; Wang, Huajun; McCarthy, Maggie; Dull, Peter M; Borrow, Ray

2014-12-13

Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMen

Safety of Combination of a Tetravalent Meningococcal Conjugate Vaccine Against Serogroups A, C, Y, W-135 With Other Vaccine Preparations: a Prospective Study of a Series of Cases Among Healthy Children and Children With Various Health Abnormalities

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Leyla S. Namazova-Baranova

2017-01-01

Full Text Available Meningococcal infection is an acute disease caused by Neisseria meningitidis, which proceeds with a diverse clinical aspect from nasopharyngitis to meningococcal meningitis and meningococcemia. Since 2014, a tetravalent meningococcal conjugate vaccine has been registered in Russia. This vaccine creates protection against serogroups A, C, W-135, Y and can be used from the age of nine months to 55 years. The actual issue is a vaccine tolerability, including when combined with other vaccine preparations.Objective: Our aim was to evaluate the safety of a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y and W-135 when it is combined with other vaccine preparations.Methods. A prospective full-design study assessed the tolerability of immunization with a meningococcal conjugate vaccine, both in case of monovaccination and in combination with a pneumococcal 13-valent conjugate vaccine, measles-mumps-rubella, viral hepatitis A, influenza, and chicken pox vaccines.Results. 97 children aged from 9 months to 18 years were vaccinated, 20 of them were healthy and 77 had medical issues (with allergic pathology, ENT diseases, cardiovascular and nervous system diseases, lung diseases as well as orphan diseases. Among vaccinated children, general reactions were observed in 3/97 (3.1% children, local reactions — in 5 (5.2%. The post-vaccination period passed asymptomatically and uneventfully in the prevailing majority of children vaccinated with a tetravalent meningococcal conjugate vaccine (in 91, 93.8%.Conclusion. The immunization with a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y, W-135 is well tolerated, both in case of monovaccination and in combination with other vaccine preparations, in healthy children of different age groups and in patients with different health status.

The role of economic evaluation in vaccine decision making : Focus on meningococcal group C conjugate vaccine

NARCIS (Netherlands)

Welte, R.; Trotter, C.L.; Edmunds, W.J.; Postma, Maarten; Beutels, P.H.

2005-01-01

In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic

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

Science.gov (United States)

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.

Clonal replacement and expansion among invasive meningococcal isolates of serogroup W in France.

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Hong, Eva; Barret, Anne-Sophie; Terrade, Aude; Denizon, Mélanie; Antona, Denise; Aouiti-Trabelsi, Myriam; Deghmane, Ala-Eddine; Parent du Châtelet, Isabelle; Levy-Bruhl, Daniel; Taha, Muhamed-Kheir

2018-02-01

Neisseria meningitidis group W (NmW) belonging to the clonal complex ST-11 (NmW/cc11) spread in Europe and in France in 2000 and declined thereafter. In France, invasive meningococcal disease (IMD) due to NmW increased again in 2012 and thereafter since 2015. Several sub-lineages of NmW/cc11 are circulating worldwide with successive epidemic waves. We aimed to describe recent epidemiological trends of NmW in France and to explore the microbiological and epidemiological characteristics associated with different NmW/cc11 sub-lineages. The epidemiology of NmW was described based on data collected through mandatory notification of IMD and strain typing data for culture-confirmed and PCR-confirmed cases for the period 2000-2016. All culture-confirmed cases due to NmW from the period 2010-2016 were characterised by whole genome sequencing (WGS). A detailed epidemiological analysis was performed for culture-confirmed cases on the basis of WGS data. During the period 2010-2016, genotyping was obtained for 148 cases including all the 132 culture-confirmed cases, among which 127 were matched with epidemiological data, and 16 PCR-confirmed cases (out of a total of 47 PCR-confirmed cases). An increase in IMD was observed in 2012 and was linked to isolates belonging to the "Anglo-French-Hajj" sub-lineage. These isolates have decreased significantly since 2013 and have been replaced by NmW/cc11 isolates related to the "South American - UK" sub-lineage which caused a marked increase in the number of cases of NmW in 2016. In this sub-lineage, the "original UK strain" was first detected in 2012 and increased thereafter, followed by the recently described "UK 2013-strain". Isolates related to the "South American-UK" sub-lineage represented 45% of all NmW cultured isolates from the whole period 2010-2016 but were the most frequent isolates in 2016, representing 76% of the total NmW typed isolates and 94% of the typed NmW/cc11 isolates. A changing pattern in the epidemiology of Nm

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

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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

Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults.

OpenAIRE

Anderson, E L; Bowers, T; Mink, C M; Kennedy, D J; Belshe, R B; Harakeh, H; Pais, L; Holder, P; Carlone, G M

1994-01-01

A meningococcal vaccine containing group A and C polysaccharides conjugated to CRM197 was evaluated in 50 adults. Vaccinees were entered into one of five groups: 30 adults received a single dose of either 22, 11, or 5.5 micrograms of the conjugated A-C vaccine; 10 received an approved meningococcal vaccine; and 10 received saline injections. Local and systemic reactions to vaccines were recorded, and immune responses were determined. The experimental meningococcal vaccine was well tolerated, ...

The influence of IS1301 in the capsule biosynthesis locus on meningococcal carriage and disease.

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Elisabeth Kugelberg

2010-02-01

Full Text Available Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR of serogroup C Neisseria meningitidis (MenC isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB from clonal complex 269 (cc269. Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.

Vaccines for the prevention of meningococcal capsular group B disease: What have we recently learned?

Science.gov (United States)

Findlow, Jamie

2016-01-01

Meningococcal disease remains a feared and devastating cause of sepsis and meningitis. Disease incidence is highest among infants and children although a significant burden of disease is experienced by adolescents, young adults and those with specific risk-factors. Prevention of disease against capsular groups A, C, W and Y; 4 of the 5 most pathogenic groups is achievable using capsular polysaccharide vaccines. It has only recently been possible to provide protection against capsular group B (MenB) strains following the licensure of a 4 component group B vaccine (4CMenB) in Europe in 2013. Following licensure, 4CMenB has been used in specific at-risk groups and in response to outbreaks of MenB disease. The largest outbreak interventions have been in students at 2 universities in the United States and for all individuals aged 2 months to 20 years of age in Quebec, Canada. The vaccine was recommended in February 2014 for implementation into the UK infant schedule at 2, 4 and 12 months of age, although it has taken over 12 months to resolve procurement discussions to enable implementation. The UK recommendation incorporates prophylactic paracetamol with infant doses when 4CMenB is administered concomitantly with routine vaccines. This is based on recent data demonstrating the ability of paracetamol to reduce fever rates to background levels without impacting immunogenicity. Post-implementation surveillance will be important to provide vaccine efficacy data as this was not possible to determine in pre-licensure studies due to the relative infrequency of MenB cases.

Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review.

Science.gov (United States)

Perry, Caroline M

2013-05-01

The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the Hib

Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands.

Directory of Open Access Journals (Sweden)

Hiltsje Hepkema

Full Text Available BACKGROUND: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY was licensed for use in subjects of 12 months of age and above. OBJECTIVES: To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine. METHODS: A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER was estimated for the current disease incidence and for a scenario when herd immunity is lost. RESULTS: Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving. CONCLUSIONS: Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity.

Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

DEFF Research Database (Denmark)

Martens, Pernille; Worm, Signe Westring; Lundgren, Bettina

2004-01-01

Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited.Martens P, Worm SW, Lundgren B, Konradsen HB, Benfield T. Department of Infectious Diseases 144, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. pernillemartens@yahoo.com BACKGROUND: Invasive infection...... with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed...

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

Science.gov (United States)

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

2016-12-20

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

Global epidemiology of serogroup B meningococcal disease and opportunities for prevention with novel recombinant protein vaccines.

Science.gov (United States)

Villena, Rodolfo; Safadi, Marco Aurelio P; Valenzuela, María Teresa; Torres, Juan P; Finn, Adam; O'Ryan, Miguel

2018-04-18

Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis.

Combination vaccine against invasive meningococcal B and pneumococcal infections: Potential epidemiological and economic impact in the Netherlands

NARCIS (Netherlands)

J.M. Bos; H.C. Rüumke (Hans); K. Welte (Karl); L. Spanjaard (Lodewijk); L. van Alphen (Loek); M.J. Postma (Maarten)

2006-01-01

textabstractBackground: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the

Invasive Paget Disease of the Vulva.

Science.gov (United States)

Borghi, Chiara; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Perotto, Stefania; Leone Roberti Maggiore, Umberto; Recalcati, Dario; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV.

Combination vaccine against invasive meningococcal B and pneumococcal infections - Potential epidemiological and economic impact in The Netherlands

NARCIS (Netherlands)

Bos, J.M.; Rumke, H.C.; Welte, R.; Spanjaard, L.; van Alphen, L.; Postma, M.J.

2006-01-01

Background: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases

A functional single nucleotide polymorphism in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease

NARCIS (Netherlands)

Kremer Hovinga, J. A.; Franco, R. F.; Zago, M. A.; ten Cate, Hugo; Westendorp, R. G. J.; Reitsma, P. H.

2004-01-01

In meningococcal sepsis, disseminated intravascular coagulation with deposition of fibrin and formation of microthrombi occurs in various organs and enhanced inhibition of fibrinolysis is associated with adverse outcome. Recently, TAFI (thrombin-activatable fibrinolysis inhibitor) was identified as

Combination vaccine against invasive meningococcal B and pneumococcal infections: potential epidemiological and economic impact in the Netherlands

NARCIS (Netherlands)

Bos, Jasper M.; Rümke, Hans C.; Welte, Robert; Spanjaard, Lodewijk; van Alphen, Loek; Postma, Maarten J.

2006-01-01

Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases occur in

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

Science.gov (United States)

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.

Crystal structure of an Anti-meningococcal subtype P1.4 PorA antibody provides basis for peptide-vaccine design

NARCIS (Netherlands)

Oomen, Clasien J.; Hoogerhout, Peter; Kuipers, Betsy; Vidarsson, Gestur; van Alphen, Loek; Gros, Piet

2005-01-01

In various western countries, subtype P1.4 of Neisseria meningitidis serogroup B causes the greatest incidence of meningococcal disease. To investigate the molecular recognition of this subtype, we crystallised a peptide (P1HVVVNNKVATH(P11)), corresponding to the subtype P1.4 epitope sequence of

Differential expression of hemoglobin receptor, HmbR, between carriage and invasive isolates of Neisseria meningitidis contributes to virulence: lessons from a clonal outbreak.

Science.gov (United States)

Sevestre, Julien; Diene, Seydina M; Aouiti-Trabelsi, Myriam; Deghmane, Ala-Eddine; Tournier, Isabelle; François, Patrice; Caron, François; Taha, Muhamed-Kheir

2018-04-11

Carriage and invasion balance in the pathogenesis of Neisseria meningitidis was analyzed during a recent clonal outbreak of meningococcal B in Normandy, France, that offered the opportunity to compare six isolates undistinguable by conventional typing (B:P1.7,16:F3-3/ST-32) isolated from invasive disease or pharyngeal asymptomatic carriage. Data from animal model (transgenic mice rendered susceptible to N. meningitidis infection) showed an absence of virulence for two non-capsulated carriage isolates, an intermediate virulence for two capsulated carriage isolates and a marked virulence for two capsulated invasive isolates. This differential pathogenesis well correlated with whole genome sequencing analysis that clustered together both isolates of each group together, forming their own arm within the Norman cluster. Gene-by-gene analysis specified that genes involved in iron acquisition were among the elements differentially represented in cluster of invasive isolates compared to cluster of capsulated carriage isolates. The hemoglobin receptor encoding gene hmbR was in an ON-phase in the capsulated invasive isolates while carriage capsulated isolates were in an OFF-phase. An ON-phase variant of a capsulated carriage isolate showed enhanced virulence. These data underline the role of phase variation (ON/OFF) of HmbR in the balance between disease isolates/carriage isolates.

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

Science.gov (United States)

Jackson, Cath; Yarwood, Joanne; Saliba, Vanessa; Bedford, Helen

2017-05-04

(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. 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. Community centres, mother and toddler groups, parents' homes and workplaces in London and Yorkshire. 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. 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. 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 written information for parents, informed by these findings. �

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

Science.gov (United States)

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

A comparison of meningococcal carriage by pregnancy status

Directory of Open Access Journals (Sweden)

Knudtson Eric J

2010-08-01

Full Text Available Abstract Neisseria meningitidis is the second leading cause of invasive meningitis. A prerequisite for infection is colonization of the nasopharynx, and asymptomatic carrier rates are widely reported in the range of 10-15%. Recent reports have indicated an increased likelihood that a pediatric admission for Neisseria meningitidis will have a mother who is pregnant in the home. We hypothesized that this association may relate to immunologic changes in pregnancy leading to higher carrier rates. We compared the carrier status by performing nasopharyngeal swabs for Neisseria meningitidis in 100 pregnant and 99 non-pregnant women. Average age of the participants was 28.9 +/- 6.7 years. The average gestational age at specimen collection was 27.5 +/- 9.4 weeks. Non pregnant women were significantly more likely to use tobacco (38% vs 24%, p The meningococcal carrier rate in our population is well below what is widely reported in the literature. Assuming a 1% carrier rate in the pregnant group and a 0.5% carrier rate in the non pregnant group, 4,763 patients would be required to detect a difference of this magnitude, given 80% power and an alpha of 0.05.

Distribution of the type III DNA methyltransferases modA, modB and modD among Neisseria meningitidis genotypes: implications for gene regulation and virulence.

Science.gov (United States)

Tan, Aimee; Hill, Dorothea M C; Harrison, Odile B; Srikhanta, Yogitha N; Jennings, Michael P; Maiden, Martin C J; Seib, Kate L

2016-02-12

Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the 'hyperinvasive lineages' are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.

Meningococcal factor H binding proteins in epidemic strains from Africa: implications for vaccine development.

Directory of Open Access Journals (Sweden)

Rolando Pajon

2011-09-01

Full Text Available Factor H binding protein (fHbp is an important antigen for vaccines against meningococcal serogroup B disease. The protein binds human factor H (fH, which enables the bacteria to resist serum bactericidal activity. Little is known about the vaccine-potential of fHbp for control of meningococcal epidemics in Africa, which typically are caused by non-group B strains.We investigated genes encoding fHbp in 106 serogroup A, W-135 and X case isolates from 17 African countries. We determined complement-mediated bactericidal activity of antisera from mice immunized with recombinant fHbp vaccines, or a prototype native outer membrane vesicle (NOMV vaccine from a serogroup B mutant strain with over-expressed fHbp. Eighty-six of the isolates (81% had one of four prevalent fHbp sequence variants, ID 4/5 (serogroup A isolates, 9 (W-135, or 74 (X in variant group 1, or ID 22/23 (W-135 in variant group 2. More than one-third of serogroup A isolates and two-thirds of W-135 isolates tested had low fHbp expression while all X isolates tested had intermediate or high expression. Antisera to the recombinant fHbp vaccines were generally bactericidal only against isolates with fHbp sequence variants that closely matched the respective vaccine ID. Low fHbp expression also contributed to resistance to anti-fHbp bactericidal activity. In contrast to the recombinant vaccines, the NOMV fHbp ID 1 vaccine elicited broad anti-fHbp bactericidal activity, and the antibodies had greater ability to inhibit binding of fH to fHbp than antibodies elicited by the control recombinant fHbp ID 1 vaccine.NOMV vaccines from mutants with increased fHbp expression elicit an antibody repertoire with greater bactericidal activity than recombinant fHbp vaccines. NOMV vaccines are promising for prevention of meningococcal disease in Africa and could be used to supplement coverage conferred by a serogroup A polysaccharide-protein conjugate vaccine recently introduced in some sub

[Study on immunogenicity of group A and group C meningococcal conjugate vaccine with coupling group B meningococcal outer membrane protein].

Science.gov (United States)

Ma, Fu-Bao; Tao, Hong; Wang, Hong-Jun

2009-10-01

To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP). 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial. 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls. The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.

Bacterial meningitis: epidemiology, herd protection, clinical characteristics, and risk assessment

NARCIS (Netherlands)

Bijlsma, M.W.

2016-01-01

This thesis studied the epidemiology of community-acquired bacterial meningitis after the nationwide implementation of paediatric conjugate vaccines, as well as the long-term epidemiology of invasive meningococcal disease and neonatal group B streptococcal disease in the Netherlands. Furthermore,

Endophthalmitis in a Child with Meningococcal Meningitis

African Journals Online (AJOL)

most obvious abnormality was that the left eye, entirely normal six hours previously, was completely opaque and appeared to be filled with thick white material. A lumbar puncture was performed, yielding cloudy CSF and, based on the microscopy and Gram stain appearance, a diagno- sis of meningococcal meningitis was ...

Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

Directory of Open Access Journals (Sweden)

Hong Sjölinder

Full Text Available Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

Science.gov (United States)

Sjölinder, Hong; Jonsson, Ann-Beth

2010-11-18

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

Science.gov (United States)

Sjölinder, Hong; Jonsson, Ann-Beth

2010-01-01

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

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

Science.gov (United States)

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.

Disseminated intravascular coagulation in meningococcal sepsis. Case 7

NARCIS (Netherlands)

Zeerleder, S.; Zürcher Zenklusen, R.; Hack, C. E.; Wuillemin, W. A.

2003-01-01

We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis.

Nerve Invasion by Epithelial Cells in Benign Breast Diseases

Directory of Open Access Journals (Sweden)

Yu-Jan Chan

2009-03-01

Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5 - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during...

NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Invasive pneumococcal disease, all ages

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, all ages - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

NNDSS - Table II. Invasive pneumococcal disease, age <5

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, age <5 - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

Invasive pests—insects and diseases

Science.gov (United States)

Donald A. Duerr; Paul A. Mistretta

2013-01-01

Key FindingsNonnative pest species have increasing impacts in the South regardless of climate change, patterns of land ownership, or changes in the composition of vegetation.“New” nonnative invasive insects and diseases will have serious impacts on southern forests over the next 50 years. Some species such as emerald ash borer...

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.

Science.gov (United States)

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 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.

Meningococcal Disease Caused by Neisseria meningitidis Serogroup B Serotype 4 in São Paulo, Brazil, 1990 to 1996

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Sacchi Claudio Tavares

1998-01-01

Full Text Available A large epidemic of serogroup B meningococcal disease (MD, has been occurring in greater São Paulo, Brazil, since 1988.21 A Cuban-produced vaccine, based on outer-membrane-protein (OMP from serogroup B: serotype 4: serosubtype P1.15 (B:4:P1.15 Neisseria meningitidis, was given to about 2.4 million children aged from 3 months to 6 years during 1989 and 1990. The administration of vaccine had little or no measurable effects on this outbreak. In order to detect clonal changes that could explain the continued increase in the incidence of disease after the vaccination, we serotyped isolates recovered between 1990 and 1996 from 834 patients with systemic disease. Strains B:4:P1.15, which was detected in the area as early as 1977, has been the most prevalent phenotype since 1988. These strains are still prevalent in the area and were responsible for about 68% of 834 serogroup B cases in the last 7 years. We analyzed 438 (52% of these strains by restriction fragment length polymorphism (RFLPs of rRNA genes (ribotyping. The most frequent pattern obtained was referred to as Rb1 (68%. We concluded that the same clone of B:4:P1.15-Rb1 strains was the most prevalent strain and responsible for the continued increase of incidence of serogroup B MD cases in greater São Paulo during the last 7 years in spite of the vaccination trial.

Minimally invasive surgical treatment of valvular heart disease.

Science.gov (United States)

Goldstone, Andrew B; Joseph Woo, Y

2014-01-01

Cardiac surgery is in the midst of a practice revolution. Traditionally, surgery for valvular heart disease consisted of valve replacement via conventional sternotomy using cardiopulmonary bypass. However, over the past 20 years, the increasing popularity of less-invasive procedures, accompanied by advancements in imaging, surgical instrumentation, and robotic technology, has motivated and enabled surgeons to develop and perform complex cardiac surgical procedures through small incisions, often eliminating the need for sternotomy or cardiopulmonary bypass. In addition to the benefits of improved cosmesis, minimally invasive mitral valve surgery was pioneered with the intent of reducing morbidity, postoperative pain, blood loss, hospital length of stay, and time to return to normal activity. This article reviews the current state-of-the-art of minimally invasive approaches to the surgical treatment of valvular heart disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Meningococcal Serogroup A, C, W-135 and Y Conjugated Vaccine : A Cost-Effectiveness Analysis in the Netherlands

NARCIS (Netherlands)

Hepkema, Hiltsje; Pouwels, Koen B.; van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

2013-01-01

Background: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W-135, Y meningococcal conjugate vaccine (MenACWY) was

A Perspective on Invasive Salmonella Disease in Africa.

Science.gov (United States)

Crump, John A; Heyderman, Robert S

2015-11-01

Salmonella enterica is a leading cause of community-acquired bloodstream infection in Africa. The contribution of typhoidal and nontyphoidal Salmonella serovars to invasive disease varies considerably in place and time, even within the same country. Nonetheless, many African countries are now thought to experience typhoid fever incidence >100 per 100,000 per year with approximately 1% of patients dying. Invasive nontyphoidal Salmonella (iNTS) disease was estimated to cause 3.4 million illnesses and 681 316 deaths in 2010, with the most disease in Africa. Antimicrobial drug resistance is a growing problem in S. enterica that threatens to further compromise patient outcomes. Reservoirs for nontyphoidal Salmonella and the predominant routes of transmission for typhoidal and nontyphoidal Salmonella are not well understood in Africa, hampering the design of evidence-based, non-vaccine- and vaccine-based prevention measures. It is difficult to distinguish clinically invasive Salmonella disease from febrile illnesses caused by other pathogens. Blood cultures are the mainstay of laboratory diagnosis, but lack sensitivity due to the low magnitude of bacteremia, do not produce results at point of care, and are not widely available in Africa. Serologic approaches to diagnosis remain inaccurate, and nucleic acid amplification tests are also compromised by low concentrations of bacteria. High-throughput whole-genome sequencing, together with a range of novel analytic pipelines, has provided new insights into the complex pattern of epidemiology, pathogenesis, and host adaptation. Concerted efforts are therefore needed to apply these new tools in the context of high-quality field surveillance to improve diagnosis, patient management, control, and prevention of invasive Salmonella infections in Africa. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Incidence of invasive Haemophilus influenzae type b disease in Italian children

International Nuclear Information System (INIS)

Tozzi, Alberto E.; Salmaso, Stefania; Atti, Marta L. Ciofi degli; Panei, Pietro; Anemona, Alessandra; Scuderi, Gabriella; Wassilak, Steven G.F.

1997-01-01

To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis. The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation. The incidence density of all invasive Hib diseases was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years. Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis. The child with sepsis died. The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries. Cost-benefit analyses are needed for planning Italian vaccination policy

Differences in the population structure of Neisseria meningitidis in two Australian states: Victoria and Western Australia.

Directory of Open Access Journals (Sweden)

Shakeel Mowlaboccus

Full Text Available Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD. A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA which are used to assign a Bexsero® antigen sequence type (BAST to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA were compared to those from the south-eastern seaboard (Victoria; VIC from 2008 to 2012. Whole-genome sequencing (WGS of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1-53.1%] was significantly lower than that in VIC (66.4% [95% CI: 62.3-70.5%]. In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the

Chronic meningococcemia: a rare presentation of meningococcal disease: case report

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Antonio Adolfo Guerra Soares Brandão

2012-03-01

Full Text Available Chronic meningococcemia is a rare clinical presentation within the spectrumof infections due to Neisseria meningitidis, which was first described in 1902.It is defined as a chronic and benign meningococcal bacteremia withoutmeningeal signs or symptoms with at least one week’s duration, characterizedby intermittent or continuous fever, polymorphic cutaneous rash, and migratoryarthropathy. The incidence is believed to be around 1:200,000 inhabitants. Itaffects predominantly young people and adults, and it is equally distributedbetween genders. Diagnosis may be challenging in the early stages of thedisease because of the difficulty in isolating Neisseria meningitidis (it reaches74% of positivity in advanced stages. Recently, the use of PCR for detectingNeisseria sp antigen in skin biopsies specimens has been considered for thoseculture-negative cases. The authors report a case of a 54-year-old femalepatient who sought medical attention for a five-day fever followed by arthralgiaand skin lesions predominantly in the lower limbs. The patient progressed toa toxemic clinical status that improved after the administration of antibiotictherapy, which consisted of oxacillin and ceftriaxone. The diagnosis of chronicmeningococcemia was performed after the isolation of Neisseria meningitidisin two different blood sample cultures. This is, to our knowledge, the firstcase of chronic meningococcemia described in Brazil (up to the writing of thisreport.

Meningococcal biofilm formation

DEFF Research Database (Denmark)

Lappann, M.; Haagensen, Janus Anders Juul; Claus, H.

2006-01-01

We show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains......, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation......X alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system....

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

Science.gov (United States)

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

Immunogenicity of meningococcal PorA antigens in OMV vaccines

NARCIS (Netherlands)

Luijkx, T.A.

2006-01-01

For the prevention of meningococcal infection caused by group B meningococci, the Netherlands Vaccine Institute (NVI) has developed a hexavalent Porin A (PorA) based Outer Membrane Vesicle (OMV) vaccine (Hexamen). In various clinical studies with HexaMen, differences in the immune responses to the

Atypical clinical presentation of meningococcal meningitis: a case report.

Science.gov (United States)

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 (nvpetechial 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.

Overcoming the Odds: Long-term psychosocial outcomes in survivors of meningococcal septic shock in childhood, and in their parents

NARCIS (Netherlands)

L.C.A.C. Vermunt (Lindy)

2008-01-01

textabstractSeptic shock, caused by Neisseria meningitidis with petechiae and/or purpura, also called Meningococcal Septic Shock (MSS), is the most serious form of meningococcal infection in early childhood. MSS is a life-threatening illness in mostly previously healthy children, with an unexpected

Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands

NARCIS (Netherlands)

Hepkema, Hiltsje; Pouwels, Koen B.; van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

2013-01-01

In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in

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.

Science.gov (United States)

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

An outbreak of meningococcal meningitis in Gauteng, Spring 1996 ...

African Journals Online (AJOL)

Objective. To describe a Neisseri.a meningitidis outbreak in Gauteng during the period 1 July to 31 December 1996. Design. A descriptive study. Setting. Patients with meningococcal meningitis in Gauteng who had been diagnosed by laboratory means, or notified during the period 1 July to 31 December 1996.

Polymorphisms in PARP, IL1B, IL4, IL10, C1INH, DEFB1, and DEFA4 in meningococcal disease in three populations.

NARCIS (Netherlands)

Emonts, M.; Vermont, C.L.; Houwing-Duistermaat, J.J.; Haralambous, E.; Gaast-de Jongh, C.E. van der; Hazelzet, J.A.; Faust, S.N.; Betts, H.; Hermans, P.W.M.; Levin, M.; Groot, R. de

2010-01-01

The pathogenesis of meningococcal infections involves activation of the complement system, proinflammatory and anti-inflammatory mediators, antimicrobial peptides, and apoptosis. We hypothesized that variations in genes encoding these products are involved in the susceptibility to and severity of

POLYMORPHISMS IN PARP, IL1B, IL4, IL10, C1INH, DEFB1, AND DEFA4 IN MENINGOCOCCAL DISEASE IN THREE POPULATIONS

NARCIS (Netherlands)

Emonts, Marieke; Vermont, Clementien L.; Houwing-Duistermaat, Jeanine J.; Haralambous, Elene; Gaast-de Jongh, Christa E.; Hazelzet, Jan A.; Faust, Saul N.; Betts, Helen; Hermans, Peter W. M.; Levin, Michael; de Groot, Ronald

The pathogenesis of meningococcal infections involves activation of the complement system, proinflammatory and anti-inflammatory mediators, antimicrobial peptides, and apoptosis. We hypothesized that variations in genes encoding these products are involved in the susceptibility to and severity of

Invasive Group A Streptococcal Disease. National Epidemiology and Genetic Analysis

NARCIS (Netherlands)

Vlaminckx, B.J.M.

2006-01-01

Infections with group A streptococci (GAS), or S. pyogenes, range from mild and superficial to very severe and lethal invasive disease. In severe invasive GAS infections, hypotension and multiorgan failure may develop rapidly resulting in the development of toxic shock-like syndrome (TSS). In the

Application of minimally invasive technique in surgical treatment of pancreatic diseases

Directory of Open Access Journals (Sweden)

ZHANG Yixi

2015-05-01

Full Text Available In recent years, with the rapid development of minimally invasive concept, from laparoscopic operation to three-dimension laparoscopic technique and to robotic surgical system, treatment modalities have changed a lot. Pancreatic diseases, including multiple lesions, have different prognoses. An appropriate surgical procedure should be selected while ensuring the radical treatment of disease, so as to minimize the injury to patients and the impairment of organ function. Minimally invasive technique is of great significance in the surgical treatment of pancreatic diseases.

Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

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Kaaijk Patricia

2012-02-01

Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.

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

Science.gov (United States)

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 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.

Immunological properties of meningococcal lipopolysaccharide from serogroups A, B & C

DEFF Research Database (Denmark)

Jensen, T J; Kharazmi, A; Shand, G

1996-01-01

The aim of the study was to measure and compare the oxidative burst, chemotaxis and cytokine production of human white blood cells, stimulated with meningococcal lipopolysaccharides (LPS) extracted from three different serogroups (A, B and C) of Neisseria meningitidis, and to evaluate whether...

Meningococcal meningitis: clinical and laboratorial characteristics, fatality rate and variables associated with in-hospital mortality

Directory of Open Access Journals (Sweden)

Vanessa L. Strelow

Full Text Available ABSTRACT Meningococcal meningitis is a public health problem. The aim of this study was to describe the clinical characteristics of patients with meningococcal meningitis, and to identify associated factors with mortality. This was a retrospective study, between 2006 and 2011, at a referral center in São Paulo, Brazil. Logistic regression analysis was used to identify factors associated with mortality. We included 316 patients. The median age was 16 years (IQR: 7–27 and 60% were male. The clinical triad: fever, headache and neck stiffness was observed in 89% of the patients. The cerebrospinal triad: pleocytosis, elevated protein levels and low glucose levels was present in 79% of patients. Factors associated with mortality in the multivariate model were age above 50 years, seizures, tachycardia, hypotension and neck stiffness. The classic clinical and laboratory triads of meningococcal meningitis were variable. The fatality rate was low. Age, seizures and shock signs were independently associated with mortality.

Vacinas meningocócicas conjugadas: eficácia e novas combinações Meningococcal conjugate vaccines: efficacy and new combinations

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Marco Aurélio Palazzi Sáfadi

2006-07-01

quadrivalente meningocócica conjugada representa, enfim, a real possibilidade de uma proteção mais abrangente contra a doença meningocócica, restando ainda a necessidade de se desenvolver uma vacina eficaz contra o meningococo B.OBJECTIVE: Meningococcal disease continues to be a serious public health concern, being associated with high morbidity and mortality rates worldwide, particularly in Brazil. In addition to discussing recent changes in the global epidemiology of meningococcal disease, we also analyze the development and impact of new conjugate vaccines on the prevention of meningococcal disease, with emphasis on the different immunization strategies implemented with these vaccines. SOURCES OF DATA: MEDLINE databases were searched from 1996 to 2006, with emphasis on review articles, clinical trials and epidemiological studies. Information was also sought on the Centers for Disease Control and Prevention, Brazilian Ministry of Health and Centro de Vigilância Epidemiológica do Estado de São Paulo websites. SUMMARY OF THE FINDINGS: Five serogroups (A, B, C, W135 and Y are responsible for virtually all cases of the disease worldwide, with marked regional and temporal differences. The new meningococcal serogroup C conjugate vaccines (MCC offer unmistakable advantages over polysaccharide vaccines. MCC vaccines generate a more efficient and long-lasting antibody response, inducing immunologic memory and reduction of nasopharyngeal carriage. The immediate results of introducing these vaccines into immunization programs have been encouraging, with a dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals (herd immunity. However, concerns have arisen regarding the long-term effectiveness of these vaccines, especially for infants vaccinated in the routine schedule. CONCLUSIONS: The reported waning of efficacy more than 1 year after routine infant immunization supports alternative schedules incorporating a

An alternative non-invasive treatment for Peyronie's disease

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Joaquim A. Claro

2004-06-01

Full Text Available OBJECTIVE: Surgical correction of the deformity and plaque caused by Peyronie's disease has some important disadvantages and extracorporeal shockwave therapy (ESWT emerged as a new promising therapy. We evaluated prospectively the efficacy and safety of the association of high dose vitamin E and ESWT as a non-invasive treatment for the disease. MATERIALS AND METHODS: Twenty-five patients 42 to 68 years old (mean = 54 presenting penile deviation and sexual distress caused by Peyronie's disease were treated in a non-invasive manner. The time of penile deviation ranged from 16 to 52 months (mean = 30. All patients had previous unsuccessful treatment for Peyronie's disease. The angulation's deformity of the penis was assessed by photography at home. The patients received vitamin E (l.200 mg daily during 3 months and underwent 3 to 6 sessions (mean = 3 of ESWT (3,000 to 4,000 shockwaves at a power level of l to 2 at 1-week intervals. RESULTS: From 25 patients treated, 16 (64% reported an improvement in penile angulation, with a mean reduction of 21 degrees (10 to 40. Eight patients reported improvement in their spontaneous erections. Overall, the patients presented only minimal bruising at the site of treatment and skin hematoma. Four patients presented urethral bleeding. The mean angulation after treatment in the control group was 48.67 degrees (30 - 70 and in the study group was 24.42 degrees (0 - 70, statistically significant. CONCLUSION: Considering the common complications and the unsatisfactory outcome of the surgical correction for Peyronie's disease, the association of high dose vitamin E and ESWT represents a good option for a non-invasive, effective and safe treatment of the penile deformity.

TGF-b2 induction regulates invasiveness of Theileria-transformed leukocytes and disease susceptibility.

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Marie Chaussepied

2010-11-01

Full Text Available Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva, or tropical theileriosis (T. annulata. Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK. We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence.

Trends in Meningococcal Meningitis Over the Past Twelve Years at ...

African Journals Online (AJOL)

Aim: To determine the trends in the occurrence of meningococcal meningitis at the University of Nigeria Teaching Hospital (UNTH) Enugu, Nigeria, as well as the antibiotic sensitivity pattern. Materials and Methods: The results of all cerebrospinal fluid samples received by the microbiology laboratory (UNTH), Enugu ...

Minimally invasive approaches for the treatment of inflammatory bowel disease

Institute of Scientific and Technical Information of China (English)

Marco Zoccali; Alessandro Fichera

2012-01-01

Despite significant improvements in medical management of inflammatory bowel disease,many of these patients still require surgery at some point in the course of their disease.Their young age and poor general conditions,worsened by the aggressive medical treatments,make minimally invasive approaches particularly enticing to this patient population.However,the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting,currently mostly pursued in high-volume referral centers,despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery.The largest body of evidence currently available for terminal ileal Crohn's disease shows improved short term outcomes after laparoscopic surgery,with prolonged operative times.For Crohn's colitis,high quality evidence supporting laparoscopic surgery is lacking.Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis.A consensus about patients' selection and the need for staging has not been reached yet.Despite the lack of conclusive evidence,a wave of enthusiasm is pushing towards less invasive strategies,to further minimize surgical trauma,with single incision laparoscopic surgery being the most realistic future development.

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

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Alies van Lier

Full Text Available Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands.The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961 and influenza (8670 DALYs/year; 95% UI: 8468-8874, which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011

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Bouwknegt, Martijn; Kretzschmar, Mirjam E.; Mangen, Marie-Josée J.; Wallinga, Jacco; de Melker, Hester E.

2016-01-01

Background Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. Methods and Findings The average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

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van Lier, Alies; McDonald, Scott A; Bouwknegt, Martijn; Kretzschmar, Mirjam E; Havelaar, Arie H; Mangen, Marie-Josée J; Wallinga, Jacco; de Melker, Hester E

2016-01-01

Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961) and influenza (8670 DALYs/year; 95% UI: 8468-8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the

Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response

NARCIS (Netherlands)

Zariri, Afshin; Beskers, Joep; van de Waterbeemd, Bas; Hamstra, Hendrik Jan; Bindels, Tim H E; van Riet, Elly; van Putten, Jos P M; van der Ley, Peter

2016-01-01

Meningococcal outer membrane vesicles (OMVs) have been extensively investigated and successfully implemented as vaccines. They contain pathogen associated molecular patterns including lipopolysaccharide (LPS), capable of triggering innate immunity. However, Neisseria meningitidis contains an

Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005–2007

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Jenney, Adam; Kado, Joseph; Good, Michael F.; Batzloff, Michael; Waqatakirewa, Lepani; Mullholland, E. Kim; Carapetis, Jonathan R.

2009-01-01

We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005–2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6–12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1–92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention. PMID:19193265

INVASIVE AMOEBIASIS COMPLICATING IFLAMMATORY BOWEL DISEASE

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Ziglam H

2007-01-01

Full Text Available INTRODUCTIONAmoebiasis, which is caused by the intestinal protozoan Entamoeba histolytica, is a ubiquitous parasitic infection affecting approximately 10% of the world’s population and causing more deaths every year (100,000 deaths than any other parasitic infection, with the exception of malaria and schistosomiasis [1–3]. Most individuals with an E. histolytica infection are asymptomatic, but some develop severe invasive disease, such as amoebic colitis. Other manifestations, such as pulmonary, cardiac or brain involvement, are rare. Intestinal amoebiasis can probably also present as a chronic, non-dysenteric syndrome of diarrhoea, weight loss, and abdominal pain that can last for years and mimic inflammatory bowel disease. Fulminant colitis with bowel necrosis leading to perforation and peritonitis occurs in only about 0.5% of cases, but it is associated with a mortality rate of more than 40%. Patients with invasive amoebiasis living in the United Kingdom and other developed countries generally acquire the infection in another country in which the pathogenic species is endemic. Areas that have high rates of amoebic infection include India, Africa, Mexico and parts of Central and South America. Infection with pathogenic E. histolytica is not a common cause of travelers’ diarrhoea, and gastrointestinal infection is uncommon in travelers who have spent less than one month in endemic areas.

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

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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

Genetic distribution of noncapsular meningococcal group B vaccine antigens in Neisseria lactamica.

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Lucidarme, Jay; Gilchrist, Stefanie; Newbold, Lynne S; Gray, Stephen J; Kaczmarski, Edward B; Richardson, Lynne; Bennett, Julia S; Maiden, Martin C J; Findlow, Jamie; Borrow, Ray

2013-09-01

The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.

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

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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.

Meningococcal serogroup B-specific responses after vaccination with bivalent rLP2086: 4 year follow-up of a randomised, single-blind, placebo-controlled, phase 2 trial.

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

2017-01-01

test strain, compared with 0% (n=0/25) to 35% (n=8/23) of control recipients. Despite initial declines in seroprotective hSBA titres for all four test strains, for three test strains (A22, A56, and B24), more than 50% of bivalent rLP2086 recipients continued to achieve titres equal to or greater than the lower limit of quantification at months 6 (57% [n=93/163] to 89% [n=42/47]), 12 (54% [n=84/155] to 69% [n=33/48]), 24 (53% [n=26/49] to 54% [n=82/152]), and 48 (51% [n=24/47] to 59% [n=79/134]); corresponding values in the control group were 14% (n=11/80) to 22% (n=5/23) at month 6, 13% (n=10/78) to 29% (n=22/76) at month 12, 16% (n=12/74) to 36% (n=8/22) at month 24, and 24% (n=16/68) to 35% (n=8/23) at month 48. For test strain B44, hSBA titres equal to or greater than the lower limit of quantification were shown in 37% (n=18/49) of vaccine recipients at 6 months, in 29% (n=14/48) at 12 months, in 22% (n=11/49) at 24 months, and in 20% (n=10/49) at 48 months, compared with 0% (n=0/25) of control recipients at month 6, 4% (n=1/25) at months 12 and 24, and 12% (n=3/25) at month 48. Adverse events were reported in seven (4%) of 170 participants in the bivalent rLP2086 group and two (3%) of 80 participants in the control group; no event was deemed related to vaccine. After three doses of bivalent rLP2086, protective hSBA titres above the correlate of protection (≥1/4) were elicited up to 4 years in more than 50% of participants for three of four meningococcal serogroup B test strains representative of disease-causing meningococci expressing vaccine-heterologous antigens. Further studies will be needed to assess possible herd immunity effects with meningococcal serogroup B vaccines and the need for a booster dose to sustain individual protection against invasive meningococcal disease. Pfizer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parents' perceived vulnerability and perceived control in preventing Meningococcal C infection: a large-scale interview study about vaccination

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van der Wal Gerrit

2008-02-01

Full Text Available Abstract Background Parents' reported ambivalence toward large-scale vaccination programs for childhood diseases may be related to their perception of the risks of side-effects or safety of vaccination and the risk of contracting the disease. The aim of this study is to evaluate parents' perceptions of their child's risk contracting a Meningococcal C infection and parents' perceived control in preventing infection in relation to their evaluation of the safety, effectiveness and usefulness of vaccination. Methods In a large-scale interview study, a random sample of parents was interviewed after their children had received vaccination against Meningococcal C in a catch-up campaign. Questions were asked about the perceived relative vulnerability of their child contracting an infection, perceived control in preventing an infection, and parents' evaluation of the safety, usefulness and effectiveness of vaccination. Results 61% of 2910 (N = 1763 parents who were approached participated. A higher perceived relative vulnerability of their own child contracting the disease was related to a more positive evaluation of the vaccination campaign, while a lower perceived vulnerability did not result in a more negative evaluation. A higher perceived control in being able to prevent an infection was, however, related to a more critical attitude toward the safety, usefulness and effectiveness of vaccination. Conclusion Perceived relative vulnerability contracting an infection and parents' perceived control in preventing an infection seem to influence parents' evaluation of the vaccination programme. Future studies should determine if, and under which circumstances, these perceptions also affect parents' vaccination behaviour and would be relevant to be taken into account when educating parents about vaccination.

Diagnosis and treatment of invasive fungal diseases in patients with severe liver diseases

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ZANG Hong

2016-09-01

Full Text Available Invasive fungal diseases (IFDs are an important factor affecting the prognosis of patients with severe liver diseases, and their early diagnosis remains a challenge for clinicians. The four most commonly seen IFDs are candidiasis, aspergillosis, cryptococcosis, and pneumocystis pneumonia. We should pay attention to the risk of developing IFDs in patients with severe liver diseases during clinical management. Particularly, early diagnosis and proper treatment of IFDs are important in high-risk patients. These are vital to improving the prognosis of patients with severe liver diseases.

Emerging clinical experience with vaccines against group B meningococcal disease.

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Wilkins, A L; Snape, M D

2017-08-01

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

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

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

2012-08-01

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

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

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

2017-12-14

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

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

Science.gov (United States)

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

2009-03-04

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

Meningococcal Infection in Children in the Krasnoyarsk Territory: Analysis of Fatal Outcomes

Directory of Open Access Journals (Sweden)

G. P. Martynova

2015-01-01

Full Text Available Meningococcal infection (MI for many years has occupied one of the most important places in the structure of acute neuroinfections in children. Some decline in MI morbidity in recent years has reduced the alertness of doctors to early detection of the disease that in some cases becomes the cause of late hospitalization, developmentof decompensated shock and ineffective resuscitation. The purpose of the given research is to identify the causes of deaths from generalized forms of MI and the prospects of mortality reduction. The paper gives the expert analysis of 22 medical histories of children who died of generalized forms of MI during the period from 2005 to 2014 in Krasnoyarsk. The work describes the features of the clinical picture of MI generalized forms in children at the present stage, reveals the causes of deaths during the period of sporadic morbidity in the Krasnoyarsk Territory and determines the adverse prognostic features that indicate the particular severity and the development of fulminant course of the disease.

Minimally Invasive Procedures - Direct and Video-Assisted Forms in the Treatment of Heart Diseases

International Nuclear Information System (INIS)

Castro, Josué Viana Neto; Melo, Emanuel Carvalho; Silva, Juliana Fernandes; Rebouças, Leonardo Lemos; Corrêa, Larissa Chagas; Germano, Amanda de Queiroz; Machado, João José Aquino

2014-01-01

Minimally invasive cardiovascular procedures have been progressively used in heart surgery. To describe the techniques and immediate results of minimally invasive procedures in 5 years. Prospective and descriptive study in which 102 patients were submitted to minimally invasive procedures in direct and video-assisted forms. Clinical and surgical variables were evaluated as well as the in hospital follow-up of the patients. Fourteen patients were operated through the direct form and 88 through the video-assisted form. Between minimally invasive procedures in direct form, 13 had aortic valve disease. Between minimally invasive procedures in video-assisted forms, 43 had mitral valve disease, 41 atrial septal defect and four tumors. In relation to mitral valve disease, we replaced 26 and reconstructed 17 valves. Aortic clamp, extracorporeal and procedure times were, respectively, 91,6 ± 21,8, 112,7 ± 27,9 e 247,1 ± 20,3 minutes in minimally invasive procedures in direct form. Between minimally invasive procedures in video-assisted forms, 71,6 ± 29, 99,7 ± 32,6 e 226,1 ± 42,7 minutes. Considering intensive care and hospitalization times, these were 41,1 ± 14,7 hours and 4,6 ± 2 days in minimally invasive procedures in direct and 36,8 ± 16,3 hours and 4,3 ± 1,9 days in minimally invasive procedures in video-assisted forms procedures. Minimally invasive procedures were used in two forms - direct and video-assisted - with safety in the surgical treatment of video-assisted, atrial septal defect and tumors of the heart. These procedures seem to result in longer surgical variables. However, hospital recuperation was faster, independent of the access or pathology

Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

Science.gov (United States)

Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

2012-09-01

The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

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

Science.gov (United States)

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

Science.gov (United States)

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

Non-invasive examination method for cerebrovascular diseases

International Nuclear Information System (INIS)

Chiba, Kazuo

1979-01-01

CT is superior in the diagnosis of the characteristics and the region of cerebrovascular diseases (CVD) to the examination with RI. The RI examination can only demonstrate the cerebrovascular diseases with large area disturbance of the cerebral cortex, that passed some days after the attack. Moreover, it is difficult to detect the small lesions or the lesions localized in the deep area such as the basal nucleus and the internal capsule by this method. A slight decrease and retardation in unilateral cerebral blood flow (under 20%, within 1.5 second) found by RI-angiography does not always indicate the side of the lesion of cerebrovascular diseases. It is expected that non-invasive examination method for CVD is improved more, and that more precise estimation method for regional cerebral circulation is developed. (Tsunoda, M.)

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.

Science.gov (United States)

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 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 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 with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Circumvention of herd immunity during an outbreak of meningococcal disease could be correlated to escape mutation in the porA gene of Neisseria meningitidis.

Science.gov (United States)

Taha, M K; Bichier, E; Perrocheau, A; Alonso, J M

2001-03-01

Meningococcal strains isolated during an outbreak were shown to belong to the ET-5 complex and to harbor a mutation in the VR2 region of the porA gene. They were less susceptible to the bactericidal effect of normal human serum than was the ET-5 wild-type strain. These results are of concern, as PorA is a potential target in vaccine design.

From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak.

Science.gov (United States)

Caron, François; du Châtelet, Isabelle Parent; Leroy, Jean-Philippe; Ruckly, Corinne; Blanchard, Myriam; Bohic, Nicole; Massy, Nathalie; Morer, Isabelle; Floret, Daniel; Delbos, Valérie; Hong, Eva; Révillion, Martin; Berthelot, Gilles; Lemée, Ludovic; Deghmane, Ala-Eddine; Bénichou, Jacques; Lévy-Bruhl, Daniel; Taha, Muhamed-Kheir

2011-06-01

Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1-5 years), safety, and epidemiological effect of the vaccination were assessed. 26,014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1-5 years). 16,709 (64%) received a complete vaccination schedule of whom 13,589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100,000 to 5·9 per 100,000; p=0·001). The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-membrane-vesicle vaccines can be effective against various strains. French Ministry of Health. Copyright © 2011 Elsevier Ltd. All rights reserved.

Correlation of group C meningococcal conjugate vaccine response with B- and T-lymphocyte activity.

Directory of Open Access Journals (Sweden)

James B Wing

Full Text Available Despite the success of conjugate vaccination against meningococcal group C (MenC disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation.

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

Science.gov (United States)

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.

Using the internet to trace contacts of a fatal meningococcemia case-New York City, 2010.

Science.gov (United States)

Gounder, Prabhu; Del Rosso, Paula; Adelson, Stephan; Rivera, Caroline; Middleton, Kathy; Weiss, Don

2012-01-01

In August 2010, the New York City Department of Health and Mental Hygiene (DOHMH) conducted an investigation to identify and provide antibiotic prophylaxis to close contacts of a patient who had died of invasive meningococcal disease. Traditional contact tracing, which relies on interviews with the patient's close associates, identified 3 persons meeting prophylaxis criteria. In addition, DOHMH learned of an Internet site used by the patient to arrange anonymous sexual encounters. By working with the Internet site administrator through a liaison, DOHMH sent notification to 15 additional persons potentially at risk for meningococcal disease; of those, at least 1 met prophylaxis criteria. The Internet has been used previously for partner notification by sexually transmitted disease control programs. This case report illustrates how the Internet can aid contact investigations for other communicable diseases, especially when identifying potential contacts is urgent, patients have died, or contacts are unknown to the patient's associates.

Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

DEFF Research Database (Denmark)

Lundbo, Lene F; Harboe, Zitta Barrella; Clausen, Louise N

2016-01-01

NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). METHODS: Cases with IPD and IMD and controls were identified......BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes.......86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. CONCLUSIONS: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis....

Developmental strategy fora new Group A meningococcal conjugate vaccine (MenAfriVacR).

Science.gov (United States)

Kulkarni, Prasad S; Jadhav, Suresh S; LaForce, F Marc

2017-10-19

Until recently, periodic Group A meningococcal meningitis outbreaks were a major public health problem in the sub-Saharan Africa. In 2001, the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO) and PATH, a Seattle-based NGO, and the Serum Institute of India Pvt Ltd (SIIPL) initiated discussions aimed at establishing a collaboration to develop a Group A meningococcal conjugate vaccine for this unmet medical need. Over the next 8 years the partnership made countless strategic decisions about product characteristics, raw materials, potential target populations, geographic prioritization and affordability of the vaccine to name a few. These decisions evolved into detailed plans for preclinical development, extensive field trials in Africa and India and a focused regulatory strategy specific for the Men A conjugate vaccine. Important characteristics of the process included, flexibility, transparency andeffective partnerships that included public agencies as well as private companies in Africa, Europe, the United States and India.

A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I).

Science.gov (United States)

Prymula, Roman; Esposito, Susanna; Zuccotti, Gian Vincenzo; Xie, Fang; Toneatto, Daniela; Kohl, Igor; Dull, Peter M

2014-01-01

The novel meningococcal serogroup B vaccine (4CMenB, Bexsero(®)), recently approved in Europe and Australia, may soon be included in routine infant immunization schedules, subject to guidance from national or regional recommending bodies. In the development of 4CMenB and consistent with other newly introduced vaccines, clinical studies have shown concomitant administration with routine infant vaccines induces an incremental increase in some reactions, including fever. As this may hinder acceptability, we examined the impact of prophylactic paracetamol on the occurrence of fever and other solicited reactions, as well as the immune responses to study vaccines, in a prospectively designed study. 4CMenB was administered as a 4-dose series at 2, 3, 4, and 12 months of age concomitantly with routine infant vaccines: DTaP-HBV-IPV/Hib and PCV7, with or without prophylactic paracetamol; a third group received MenC vaccine. Immune responses to 4CMenB were not decreased by the use of paracetamol prophylaxis and there were no clinically relevant effects on immune responses to routine vaccines. Occurrence of fever was higher in infants co-administered with 4CMenB compared with those given MenC vaccine, but was significantly decreased by prophylactic paracetamol, as were other solicited reactions to vaccination, both local and systemic. Co-administration of 4CMenB had an acceptable tolerability profile, with no withdrawals due to vaccination-related adverse events. Inclusion of 4CMenB in routine infant immunization schedules will be a major advance in the control of meningococcal disease, and our study indicates that by using paracetamol prophylaxis, post-vaccination reactions are reduced without clinically relevant negative consequences on vaccine immunogenicity.

Invasive Candidiasis

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... Waterborne, and Environmental Diseases Mycotic Diseases Branch Invasive Candidiasis Recommend on Facebook Tweet Share Compartir Global Emergence ... antifungal drugs. Learn more about C. auris Invasive candidiasis is an infection caused by a yeast (a ...

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

Science.gov (United States)

Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

Preventing invasive Group B Streptococcus (GBS) disease in South ...

African Journals Online (AJOL)

9 No. 3 has been successfully used for the prevention of tetanus, influenza and pertussis in infants.[11] A trivalent GBS polysaccharide-protein conjugate vaccine (against serotypes Ia, Ib and III) has completed phase-II evaluation among pregnant women and has the potential to prevent 70 - 80% of all invasive GBS disease.

Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

Science.gov (United States)

Herrera, Sabina; Husain, Shahid

2018-05-21

The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

Presentation of life-threatening invasive nontyphoidal Salmonella disease in Malawian children: A prospective observational study.

Science.gov (United States)

MacLennan, Calman A; Msefula, Chisomo L; Gondwe, Esther N; Gilchrist, James J; Pensulo, Paul; Mandala, Wilson L; Mwimaniwa, Grace; Banda, Meraby; Kenny, Julia; Wilson, Lorna K; Phiri, Amos; MacLennan, Jenny M; Molyneux, Elizabeth M; Molyneux, Malcolm E; Graham, Stephen M

2017-12-01

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and 52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%; 95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had an overlapping clinical syndrome. Presentation at Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.

Population-based surveillance for invasive pneumococcal disease in homeless adults in Toronto.

Directory of Open Access Journals (Sweden)

Agron Plevneshi

Full Text Available BACKGROUND: Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs. METHODS: We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006. RESULTS: We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001, and more likely than other adults to be smokers (95% vs. 31%, P<.001, to abuse alcohol (62% vs 15%, P<.001, and to use intravenous drugs (42% vs 4%, P<.001. Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006, but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73. The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001. In homeless adults, 28 (32% of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48% of serotypes included in the 13-valent conjugate vaccine, and 72 (83% of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population. CONCLUSIONS: Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes

Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

NARCIS (Netherlands)

Flier, M. van der; Baerveldt, E.M.; Miedema, A.; Hartwig, N.G.; Hazelzet, J.A.; Emonts, M.; Groot, R. de; Prens, E.P.; Vught, A.J. van; Jansen, N.J.

2013-01-01

OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs.

Recurrent invasive thymoma with pleural dissemination : disease management and treatment possibilities.

Science.gov (United States)

Konecna, J; Willemse, E; Lefebvre, Y; de Wind, R; Andry, G

2014-01-01

Thymoma is the most common benign neoplasm of the anterior mediastinum presenting often an agressive behaviour typical for the malignants tumors. The rate of invasive thymoma recurrency is relatively high. We present the case of a 55-year old man with a recurrent invasive thymoma with a pleural dissemination, detected on CT-imaging 2 years following his primary surgery. Since the first pre-operative imaging studies showed no invasion of the adjacent organs and a thymoma was suspected, a surgical resection was decided as a first line treatment. Per-operatively a number of adjacent structures were invaded and despite a macroscopical RO resection, the margins were microscopically positive. An invasive thymoma, WHO classification B3, Masaoka stage IVb was diagnosed and the patient received adjuvant radiotherapy. We highlight the role of multimodality treatement and disscus the potential of surgical, radiotherapeutical and systemic therapy in stage IV thymoma as well as in recurrent disease. Copyright© Acta Chirurgica Belgica.

Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

DEFF Research Database (Denmark)

Bygbjerg, I C; Hansen, M B; Rønn, A M

1997-01-01

The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study

DEFF Research Database (Denmark)

Harboe, Zitta B; Thomsen, Reimar W; Riis, Anders

2009-01-01

BACKGROUND: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD). METHODS AND FINDINGS: In a nationwide population-based...

Critical analysis of old and new vaccines against N. meningitidis serogroup C, considering the meningococcal disease epidemiology in Brazil Análise crítica das antigas e novas vacinas contra a N. meningitidis do sorogrupo C, considerando a epidemiologia da doença meningocócica no Brasil

Directory of Open Access Journals (Sweden)

Lucia Ferro Bricks

2003-01-01

Full Text Available Worldwide, the impact of meningococcal disease is substantial, and the potential for the introduction and spread of more virulent strains of N. meningitidis or strains with increased resistance to current antibiotics causes concern, making prevention essential. OBJECTIVES: Review the indications for meningococcal disease vaccines, considering the epidemiological status in Brazil. METHODS: A critical literature review on this issue using the Medline and Lilacs databases. RESULTS: In Brazil, MenB and MenC were the most important serogroups identified in the 1990s. Polysaccharide vaccines available against those serogroups can offer only limited protection for infants, the group at highest risk for meningococcal disease. Additionally, polysaccharide vaccines may induce a hypo-responsive state to MenC. New meningococcal C conjugate vaccines could partially solve these problems, but it is unlikely that in the next few years a vaccine against MenB that can promote good protection against multiple strains of MenB responsible for endemic and epidemic diseases will become available. CONCLUSIONS: In order to make the best decision about recommendations on immunization practices, better quality surveillance data are required. In Brazil, MenC was responsible for about 2,000 cases per year during the last 10 years. New conjugate vaccines against MenC are very effective and immunogenic, and they should be recommended, especially for children less than 5 years old. Polysaccharide vaccines should be indicated only in epidemic situations and for high-risk groups. Until new vaccines against MenC and MenB are available for routine immunization programs, the most important measure for controlling meningococcal disease is early diagnosis of these infections in order to treat patients and to offer chemoprophylaxis to contacts.Em todo o mundo, o impacto das doenças meningocócicas é enorme e o potencial para a introdução e disseminação de cepas da N

Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study.

Science.gov (United States)

Petousis-Harris, Helen; Paynter, Janine; Morgan, Jane; Saxton, Peter; McArdle, Barbara; Goodyear-Smith, Felicity; Black, Steven

2017-09-30

Gonorrhoea is a major global public health problem that is exacerbated by drug resistance. Effective vaccine development has been unsuccessful, but surveillance data suggest that outer membrane vesicle meningococcal group B vaccines affect the incidence of gonorrhoea. We assessed vaccine effectiveness of the outer membrane vesicle meningococcal B vaccine (MeNZB) against gonorrhoea in young adults aged 15-30 years in New Zealand. We did a retrospective case-control study of patients at sexual health clinics aged 15-30 years who were born between Jan 1, 1984, and Dec 31, 1998, eligible to receive MeNZB, and diagnosed with gonorrhoea or chlamydia, or both. Demographic data, sexual health clinic data, and National Immunisation Register data were linked via patients' unique personal identifier. For primary analysis, cases were confirmed by laboratory isolation or detection of Neisseria gonorrhoeae only from a clinical specimen, and controls were individuals with a positive chlamydia test only. We estimated odds ratios (ORs) comparing disease outcomes in vaccinated versus unvaccinated participants via multivariable logistic regression. Vaccine effectiveness was calculated as 100×(1-OR). 11 of 24 clinics nationally provided records. There were 14 730 cases and controls for analyses: 1241 incidences of gonorrhoea, 12 487 incidences of chlamydia, and 1002 incidences of co-infection. Vaccinated individuals were significantly less likely to be cases than controls (511 [41%] vs 6424 [51%]; adjusted OR 0·69 [95% CI 0·61-0·79]; pvaccine effectiveness of MeNZB against gonorrhoea after adjustment for ethnicity, deprivation, geographical area, and sex was 31% (95% CI 21-39). Exposure to MeNZB was associated with reduced rates of gonorrhoea diagnosis, the first time a vaccine has shown any protection against gonorrhoea. These results provide a proof of principle that can inform prospective vaccine development not only for gonorrhoea but also for meningococcal vaccines. GSK

Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

DEFF Research Database (Denmark)

Weis, N; Lind, I

1998-01-01

In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogro......, and as applied in the study MEE was superior to DNA fingerprinting. Clusters of invasive strains were reliably identified by phenotyping alone, whereas determination of identity of carrier strains and an invasive strain required genotyping.......In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...

Non invasive diagnostic methods for better screening of peripheral arterial disease.

Science.gov (United States)

Nirala, Neelamshobha; Periyasamy, R; Kumar, Awanish

2018-05-16

Peripheral arterial disease (PAD) is a common circulatory problem in which narrowed arteries reduce blood flow to extremities usually legs. It does not receive enough blood flow to keep up with demand. This causes symptoms, most notably leg pain while walking which is known as claudication. It is a common manifestation of type II Diabetes, but the relationship between other vascular diseases and lower limb (LL)-PAD has been poorly understood and investigated. When assessing a patient with clinically LLPAD, two questions are in order to establish a diagnosis: one is non-invasive testing and other is invasive. Invasive methods are painful and get so bad that some people need to have a leg surgery. People with Diabetes are at increased risk for amputation and it is used only when the damage is very severe. Diagnosis of LLPAD begins with a physical examination, patient history, certain questionnaire and non invasive mode of diagnosis is started for the screening of patients. Clinicians check for weak pulses in the legs and then decide for further diagnosis. Paper discusses the prevalence of LLPAD worldwide and in India along with the clinical effectiveness and limitations of these methods in case of Diabetes. The focus of this review is to discuss only those non invasive methods which are widely used for screening of LLPAD like Ankle brachial index (ABI), Toe brachial Index (TBI), and use of photoplethysmogram (PPG) specially in case of Diabetic patients. Also, this paper gives an overview of the work done using ABI, TBI, and PPG for detection of LLPAD. These tests are not painful and could be performed in a cost-effective manner to avoid delays in screening/diagnosis and also reduce costs. Copyright © 2018. Published by Elsevier Inc.

Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study.

Directory of Open Access Journals (Sweden)

Stefan Flasche

2011-04-01

Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

Invasive candidosis: contrasting the perceptions of infectious disease physicians and intensive care physicians

Directory of Open Access Journals (Sweden)

Vanessa Schultz

2013-07-01

Full Text Available Introduction We analyze how infectious disease physicians perceive and manage invasive candidosis in Brazil, in comparison to intensive care unit specialists. Methods A 38-question survey was administered to 56 participants. Questions involved clinicians' perceptions of the epidemiology, diagnosis, treatment and prophylaxis of invasive candidosis. P < 0.05 was considered statistically significant. Results The perception that candidemia not caused by Candida albicans occurs in less than 10% of patients is more commonly held by intensive care unit specialists (p=0.018. Infectious disease physicians almost always use antifungal drugs in the treatment of patients with candidemia, and antifungal drugs are not as frequently prescribed by intensive care unit specialists (p=0.006. Infectious disease physicians often do not use voriconazole when a patient's antifungal treatment has failed with fluconazole, which also differs from the behavior of intensive care unit specialists (p=0.019. Many intensive care unit specialists use fluconazole to treat candidemia in neutropenic patients previously exposed to fluconazole, in contrast to infectious disease physicians (p=0.024. Infectious disease physicians prefer echinocandins as a first choice in the treatment of unstable neutropenic patients more frequently than intensive care unit specialists (p=0.013. When candidemia is diagnosed, most infectious disease physicians perform fundoscopy (p=0.015, whereas intensive care unit specialists usually perform echocardiograms on all patients (p=0.054. Conclusions This study reveals a need to better educate physicians in Brazil regarding invasive candidosis. The appropriate management of this disease depends on more drug options being available in our country in addition to global coverage in private and public hospitals, thereby improving health care.

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

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Levy, C; Bechet, S; Cohen, R

2016-01-01

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

Immunodeficiency among children with recurrent invasive pneumococcal disease

DEFF Research Database (Denmark)

Ingels, Helene; Schejbel, Lone; Lundstedt, A C

2015-01-01

examined. RESULTS: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response......BACKGROUND: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory......-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. METHODS: Cases of rIPD in children 0-15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer...

Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

Science.gov (United States)

Werno, Anja M; Murdoch, David R

2008-03-15

The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

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

Science.gov (United States)

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.

[S. Pyogenes invasive disease in a paediatric hospital: 1996-2009].

Science.gov (United States)

Caetano, Joana Serra; Neto, Paula; Alves, Manuela Costa; Rodrigues, Fernanda

2010-01-01

S. pyogenes is among the most common bacteria in Pediatrics, and is associated with a wide variety of infections and large range of severity. The aim was to evaluate trends of Group A Streptococcal invasive disease in a paediatric tertiary hospital. Retrospective analyses of the medical records of all children with group A streptococcal invasive disease (positive culture obtained from sterile sites), from January 1996 to December 2009 (14 years). There were 24 cases, with a maximum of four cases/year. Eighteen cases (75%) ocurred in the second half of the study. Sixty-seven percent were boys and the median age was three years. The most frequent clinical manifestations were fever (79%), rash (54%) and arthalgia/limbs' pain (46%). The diagnoses were bacteriemia (six), osteoarticular infection (five), celulitis (three), pyomyositis, mastoiditis, surgical wound infection, toxic shock syndrome (two each), necrotizing fasciitis and pneumonia (one each). Four cases occurred during the course of varicella. Other risk factors were present in six cases. Median neutrophyl count was 10.690 x 105/L (2.013-19.180 x 105/L) and median C reactive protein was 146 mg/L (3-425 mg/L). Bacteria were isolated mainly from blood (71%). The outcome was good for most cases but there were two deaths due to toxic shock syndrome. M typing and the presence of virulence factors genes were not assessed. Although the number is small, there was an increase of S. pyogenes invasive disease in the second half of the study. Several cases occurred in the course of varicela or in the presence of other risk factors. Fatal outcome was associated with two toxic shock syndrome cases. Microbiological investigation is essential to understand which M types or virulence factors genes are involved.

Meningitis Myths and Facts

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... Diseases Infographic Prevention and Control of Meningococcal Disease Meningitis Myths and Facts Myth: Meningococcal disease is easy ... infected person, such as shaking hands. Fact: Meningococcal meningitis is spread through air droplets and direct contact ...

A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2–10 years

Science.gov (United States)

Vesikari, Timo; Forstén, Aino; Boutriau, Dominique; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M.

2012-01-01

Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2–10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2–10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NCT00427908. PMID:23032168

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

Science.gov (United States)

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.

Perineural Invasion is a Marker for Pathologically Advanced Disease in Localized Prostate Cancer

International Nuclear Information System (INIS)

Lee, Irwin H.; Roberts, Rebecca; Shah, Rajal B.; Wojno, Kirk J.; Wei, John T.; Sandler, Howard M.

2007-01-01

Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy

Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

National Research Council Canada - National Science Library

Drabick, Joseph

1998-01-01

An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

Resurgence of Neisseria meningitidis serogroup W ST-11 (cc11) in Madagascar, 2015-2016.

Science.gov (United States)

Rasoanandrasana, Saïda; Raberahona, Mihaja; Milenkov, Milen; Rakotomahefa Narison, Mbolanirina Lala; Ranaivo Rabetokotany, Felana; Rakotovao, Luc; Randria, Mamy Jean de Dieu; Hong, Eva; Paranhos-Baccalà, Glaucia; Taha, Muhamed-Kheir; Rakoto-Andrianarivelo, Mala

2017-02-01

The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder.

Science.gov (United States)

Laursen, Thomas Munk; Munk-Olsen, Trine; Agerbo, Esben; Gasse, Christiane; Mortensen, Preben Bo

2009-07-01

Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess

Treatment and prevention of invasive pneumococcal disease.

Science.gov (United States)

Domínguez-Alegría, A R; Pintado, V; Barbolla, I

2018-02-12

Invasive pneumococcal disease is a severe infection that mainly affects patients with associated comorbidity. The paediatric conjugate vaccination has resulted in a change in the adult vaccination strategy. The antibiotic resistance of pneumococcus is not currently a severe problem. Nevertheless, the World Health Organisation has included pneumococcus among the bacteria whose treatment requires the introduction of new drugs, such as ceftaroline and ceftobiprole. Although the scientific evidence is still limited, the combination of beta-lactams and macrolides is recommended as empiric therapy for bacteraemic pneumococcal pneumonia. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Recurrent severe invasive pneumococcal disease in an adult with previously unknown hyposplenia

DEFF Research Database (Denmark)

Ballegaard, Vibe C; Schejbel, Lone; Hoffmann, Steen

2015-01-01

was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of severe......BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode...... of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and apparently...

Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

International Nuclear Information System (INIS)

Sanchez-Pernaute, Rosario; Brownell, Anna-Liisa; Jenkins, Bruce G.; Isacson, Ole

2005-01-01

Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders

The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection.

Directory of Open Access Journals (Sweden)

Ana Antunes

Full Text Available Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP:sugar phosphotransferase system (PTS, in which the phosphocarrier protein HPr (encoded by the ptsH gene plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and ΔptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the ΔptsH strain. The ΔptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the ΔptsH mutant. We therefore compared the transcriptomic profiles of wild-type and ΔptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43% and several membrane-associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the ΔptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the ΔptsH strain from blood.

Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4

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Can Boğa

2015-06-01

Full Text Available This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.

Non-invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease.

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Caboot, Jason B; Jawad, Abbas F; McDonough, Joseph M; Bowdre, Cheryl Y; Arens, Raanan; Marcus, Carole L; Mason, Thornton B A; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L

2012-08-01

Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and -0.22% for MetHb. The precision of the measured SpCO was ± 2.1% within a COHb range of 0.4-6.1%, and the precision of the measured SpMet was ± 0.33% within a MetHb range of 0.1-1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. Copyright © 2012 Wiley Periodicals, Inc.

Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?

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Hong, Eva; Giuliani, Marzia Monica; Deghmane, Ala-Eddine; Comanducci, Maurizio; Brunelli, Brunella; Dull, Peter; Pizza, Mariagrazia; Taha, Muhamed-Kheir

2013-02-04

A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX outbreaks in Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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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

Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice.

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Belkacem, Nouria; Bourdet-Sicard, Raphaëlle; Taha, Muhamed-Kkeir

2018-04-10

The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection. We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated. Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs. Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.

Advances in invasive evaluation and treatment of patients with ischemic heart disease

NARCIS (Netherlands)

Hoeven, Barend Leendert van der

2008-01-01

The aim of this thesis was to evaluate new developments in the treatment of patients with ischemic heart disease, with special focus to the invasive evaluation of plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) and treatment of STEMI patients with

Recurrent Invasive Pneumococcal Disease Serotype 12F in a Vaccinated Splenectomized Patient

DEFF Research Database (Denmark)

Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn

2016-01-01

This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded...

A gonococcal homologue of meningococcal γ-glutamyl transpeptidase gene is a new type of bacterial pseudogene that is transcriptionally active but phenotypically silent

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Watanabe Haruo

2005-10-01

Full Text Available Abstract Background It has been speculated that the γ-glutamyl transpeptidase (ggt gene is present only in Neisseria meningitidis and not among related species such as Neisseria gonorrhoeae and Neisseria lactamica, because N. meningitidis is the only bacterium with GGT activity. However, nucleotide sequences highly homologous to the meningococcal ggt gene were found in the genomes of N. gonorrhoeae isolates. Results The gonococcal homologue (ggt gonococcal homologue; ggh was analyzed. The nucleotide sequence of the ggh gene was approximately 95 % identical to that of the meningococcal ggt gene. An open reading frame in the ggh gene was disrupted by an ochre mutation and frameshift mutations induced by a 7-base deletion, but the amino acid sequences deduced from the artificially corrected ggh nucleotide sequences were approximately 97 % identical to that of the meningococcal ggt gene. The analyses of the sequences flanking the ggt and ggh genes revealed that both genes were localized in a common DNA region containing the fbp-ggt (or ggh-glyA-opcA-dedA-abcZ gene cluster. The expression of the ggh RNA could be detected by dot blot, RT-PCR and primer extension analyses. Moreover, the truncated form of ggh-translational product was also found in some of the gonococcal isolates. Conclusion This study has shown that the gonococcal ggh gene is a pseudogene of the meningococcal ggt gene, which can also be designated as Ψggt. The gonococcal ggh (Ψggt gene is the first identified bacterial pseudogene that is transcriptionally active but phenotypically silent.

Using the 4 Pillars™ Practice Transformation Program to increase adolescent human papillomavirus, meningococcal, tetanus-diphtheria-pertussis and influenza vaccination.

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Zimmerman, Richard K; Raviotta, Jonathan M; Nowalk, Mary Patricia; Moehling, Krissy K; Reis, Evelyn Cohen; Humiston, Sharon G; Lin, Chyongchiou Jeng

2017-10-27

To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population. Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016). Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination. Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program

Antigen sequence typing of outer membrane protein (fetA gene of Neisseria meningitidis serogroup A from Delhi & adjoining areas

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S Dwivedi

2014-01-01

Full Text Available Background & objectives: Meningitis caused by Neisseria meningitidis is a fatal disease. Meningococcal meningitis is an endemic disease in Delhi and irregular pattern of outbreaks has been reported in India. All these outbreaks were associated with serogroup A. Detailed molecular characterization of N. meningitidis is required for the management of this fatal disease. In this study, we characterized antigenic diversity of surface exposed outer membrane protein (OMP FetA antigen of N. meningitidis serogroup A isolates obtained from cases of invasive meningococcal meningitis in Delhi, India. Methods: Eight isolates of N. meningitidis were collected from cerebrospinal fluid during October 2008 to May 2011 from occasional cases of meningococcal meningitis. Seven isolates were from outbreaks of meningococcal meningitis in 2005-2006 in Delhi and its adjoining areas. These were subjected to molecular typing of fetA gene, an outer membrane protein gene. Results: All 15 N. meningitides isolates studied were serogroup A. This surface exposed porin is putatively under immune pressure. Hence as a part of molecular characterization, genotyping was carried out to find out the diversity in outer membrane protein (FetA gene among the circulating isolates of N. meningitidis. All 15 isolates proved to be of the same existing allele type of FetA variable region (VR when matched with global database. The allele found was F3-1 for all the isolates. Interpretation & conclusions: There was no diversity reported in the outer membrane protein FetA in the present study and hence this protein appeared to be a stable molecule. More studies on molecular characterization of FetA antigen are required from different serogroups circulating in different parts of the world.

Trends in the epidemiology of invasive Haemophilus influenzae disease in Queensland, Australia from 2000 to 2013: what is the impact of an increase in invasive non-typable H. influenzae (NTHi)?

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Wan Sai Cheong, J; Smith, H; Heney, C; Robson, J; Schlebusch, S; Fu, J; Nourse, C

2015-10-01

Following the introduction of vaccination against Haemophilus influenzae type b (Hib), cases of invasive encapsulated Hib disease have decreased markedly. This study aimed to examine subsequent epidemiological trends in invasive H. influenzae disease in Queensland, Australia and in particular, assess the clinical impact and public health implications of invasive non-typable H. influenzae (NTHi) strains. A multicentre retrospective study was conducted from July 2000 to June 2013. Databases of major laboratories in Queensland including Queensland Forensic and Scientific Services (jurisdictional referral laboratory for isolate typing) were examined to identify cases. Demographic, infection site, Indigenous status, serotype, and mortality data were collected. In total, 737 invasive isolates were identified, of which 586 (79·5%) were serotyped. Hib, NTHi and encapsulated non-b strains, respectively, constituted 12·1%, 69·1% and 18·8% of isolates. The predominant encapsulated non-b strains were f (45·5%) and a (27·3%) serotypes. Of isolates causing meningitis, 48·9% were NTHi, 14·9% Hib, 14·9% Hie, 10·6% Hif, 6·4% Hia and 4·3% were untyped. During the study period, there was an increase in the incidence of invasive NTHi disease (P = 0·007) with seasonal peaks in winter and spring (P 0·001) and Hib (P = 0·039) than non-Indigenous patients. In Queensland, invasive H. influenzae disease is now predominantly encountered in adults and most commonly caused by NTHi strains with demonstrated pathogenicity extending to otherwise young or immunocompetent individuals. Routine public health notification of these strains is recommended and recent available immunization options should be considered.

Tratamiento quirúrgico de las complicaciones del shock meningocóccico grave Surgical treatment of the severe meningococcal septic shock complications

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P. Casteleiro Roca

2010-06-01

Full Text Available El shock meningocóccico es una entidad relativamente frecuente y de pronóstico muy grave, que provoca fallo multiorgánico con una alta mortalidad y que precisa ingreso en Unidad de Cuidados Intensivos. En los casos grandes puede provocar necrosis de tejidos mediante una fisiopatología poco clara. En los últimos años la supervivencia de estos pacientes ha aumentado debido al diagnóstico precoz y a medidas de reanimación más agresivas. Como consecuencia encontramos un aumento del número de pacientes con necrosis extensas de tejidos que precisan tratamiento. Lo fundamental ante el diagnóstico de un shock meningocóccico es establecer el tratamiento médico precoz con medidas de reanimación agresivas y antibioterapia. Sugerimos que la necrosis extensa de tejidos que sufren estos pacientes debe tratarse como si se tratase de un paciente quemado, realizando curas diarias con sulfadiacina argéntica y cirugías seriadas (desbridamiento - amputación - cobertura tan pronto como la situación clínica del paciente lo permita. Es necesario un seguimiento muy cercano de estos pacientes, dada la necesidad de cirugías secundarias que van a precisar a lo largo de su vida, así como la realización de pruebas de imagen para descartar la presencia de osteomielitis secundarias.Meningococcal shock is a relatively frequent disease with a serious prognosis, that causes a multiorganic failure with high mortality and Intensive Care Unit admission. Serious meningococcal shock causes tissue necrosis by uncertain physiopathology. In the last years, there is an increase of the survival, as a result of early diagnosis and aggressive resuscitation. So, there is an increase of patient's tissue necrosis that needs surgery. The most important aspect in front of meningococcal shock is to establish early medical treatment with aggressive resuscitation and antibiotics. Tissue necrosis should be treated like burn patient: argentic sulfadiazine daily cure and serial

Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

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Diez-Domingo, Javier; Gurtman, Alejandra; Bernaola, Enrique; Gimenez-Sanchez, Francisco; Martinon-Torres, Federico; Pineda-Solas, Valentin; Delgado, Alfonso; Infante-Marquez, Pilar; Liang, John Z; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

2013-11-04

Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

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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.

Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine

NARCIS (Netherlands)

Vermont, C. L.; van Dijken, H. H.; Kuipers, A. J.; van Limpt, C. J. P.; Keijzers, W. C. M.; van der Ende, A.; de Groot, R.; van Alphen, L.; van den Dobbelsteen, G. P. J. M.

2003-01-01

The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and

Epidemiological burden of invasive pneumococcal disease in children and adolescents with predisposing risk factors.

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Falleiros-Arlant, Luiza Helena; Berezin, Eitan Naaman; Avila-Aguero, Maria Luisa; Pirez, Maria Catalina; Gentile, Angela; Richardson, Vesta; Brea, Jose; Mariño, Cristina

2015-09-01

Some medical conditions constitute important risk factors for the development of invasive pneumococcal diseases in children and adolescents aged from 5 to 19 years. Conjugate vaccines have potential efficacy in this scenario, but are not available in many Latin American public healthcare systems for this age group. This study aimed to estimate the preventable fraction of invasive pneumococcal diseases among individuals aged from 5 to 19 years with associated risk factors for its development. Data regarding the Latin America population, risk factors prevalence and conjugate vaccines efficacy were obtained from the literature. Total population at risk ranged from 17.3 to 64.6 million of individuals and asthma was the most impacting risk factor. According to SIREVA, PCV13 provided a 62.9% serotypes coverage in individuals from 5 to 29 years in 2012, potentially increasing the covered population from [8,338,457-31,057,620] with PCV10 to [10,906,356-40,622,078] with PCV13. To date, according to available efficacy data, the hypothetically immunized population ranged from 11.4 to 42.4 million, representing 7.0% to 26.0% of the total population in this age group. Vaccination in risk groups should be encouraged, as it potentially contributes to the reduction in the number of cases of invasive pneumococcal disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Invasive cervical cancer accompanied by IgG4-related disease.

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Mizuno, Rin; Yamanishi, Yukio; Uda, Satoko; Terashima, Tsuyoshi; Higashi, Tatsuya; Higuchi, Toshihiro

2016-09-01

IgG4-related disease (IgG4-RD) is a systemic disease that affects multiple organs and generates nodules or thickening. Discriminating these diseases from malignancy is important because glucocorticoid treatment is effective for patients with IgG4-RD. Coexistence of IgG4-RD with various malignant diseases has been reported, but there are few reports with regard to gynecologic malignant diseases. We encountered a case of invasive cervical cancer stage IIB accompanied by IgG4-RD. The patient was a 46-year-old woman. On pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography and computed tomography, systemic multiple lymph node swelling was seen, including in the neck and the mediastinum in addition to uterine cervix. Diagnosis (and hence, appropriate treatment choice) was achieved on pathology of the submandibular gland and uterus, and analysis of serum IgG4. IgG4-RD should be suspected in patients presenting with malignancy and unusual multiple lymph node swelling. © 2016 Japan Society of Obstetrics and Gynecology.

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

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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

2015-10-01

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.

Health and economic outcomes of introducing the new MenB vaccine (Bexsero into the Italian routine infant immunisation programme.

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Marcello Tirani

Full Text Available In January 2013 a novel type of multicomponent protein-based vaccine against group B meningococcal disease was licensed by the European Medicines Agency. With the widespread use of the meningococcal serogroup C conjugate vaccines, serogroup B remains now the major cause of bacterial meningitis and septicaemia in young children in Europe. The aim of this study is to investigate the health and the economic outcomes of MenB vaccine introduction into the Italian routine mass vaccination programme.The present work is structured in two main parts. Firstly, we assess the epidemiological burden of group B meningococcal disease using official hospitalisation and notification data from two of the most populated Italian regions (Lombardia and Piemonte during a 6-year study period (2007-2012. Secondly, we evaluate the cost-effectiveness of the immunisation programme in Italy from the public health payer perspective under base case parameters assumptions and performing a comprehensive sensitivity analysis to assess the robustness and the uncertainty of our model results.MenB serotype is responsible for 59% of the 341 cases of Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB infection is estimated to be 0.21/100,000/y resulting at the highest level in children ≤4 years of age. Although the new MenB vaccine can potentially prevent about one third of the disease cases in the Italian population, model results show this strategy is unlikely to be cost-effective (ICER value over €350,000/QALY with a vaccine that prevents disease only. These results are robust under most of the sensitivity scenarios except when allowing for lower discount rates.The introduction of the novel vaccine into the routine immunisation schedule needs to be carefully evaluated. The new MenB vaccine has the potential to reduce the disease burden at the population level. However, from the Italian Health Service perspective, the immunisation programme is

Health and economic outcomes of introducing the new MenB vaccine (Bexsero) into the Italian routine infant immunisation programme.

Science.gov (United States)

Tirani, Marcello; Meregaglia, Michela; Melegaro, Alessia

2015-01-01

In January 2013 a novel type of multicomponent protein-based vaccine against group B meningococcal disease was licensed by the European Medicines Agency. With the widespread use of the meningococcal serogroup C conjugate vaccines, serogroup B remains now the major cause of bacterial meningitis and septicaemia in young children in Europe. The aim of this study is to investigate the health and the economic outcomes of MenB vaccine introduction into the Italian routine mass vaccination programme. The present work is structured in two main parts. Firstly, we assess the epidemiological burden of group B meningococcal disease using official hospitalisation and notification data from two of the most populated Italian regions (Lombardia and Piemonte) during a 6-year study period (2007-2012). Secondly, we evaluate the cost-effectiveness of the immunisation programme in Italy from the public health payer perspective under base case parameters assumptions and performing a comprehensive sensitivity analysis to assess the robustness and the uncertainty of our model results. MenB serotype is responsible for 59% of the 341 cases of Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB infection is estimated to be 0.21/100,000/y resulting at the highest level in children ≤4 years of age. Although the new MenB vaccine can potentially prevent about one third of the disease cases in the Italian population, model results show this strategy is unlikely to be cost-effective (ICER value over €350,000/QALY) with a vaccine that prevents disease only. These results are robust under most of the sensitivity scenarios except when allowing for lower discount rates. The introduction of the novel vaccine into the routine immunisation schedule needs to be carefully evaluated. The new MenB vaccine has the potential to reduce the disease burden at the population level. However, from the Italian Health Service perspective, the immunisation programme is unlikely to be

The role of pre-invasive disease in overdiagnosis: A microsimulation study comparing mass screening for breast cancer and cervical cancer.

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van Luijt, Paula A; Rozemeijer, Kirsten; Naber, Steffie K; Heijnsdijk, Eveline Am; van Rosmalen, Joost; van Ballegooijen, Marjolein; de Koning, Harry J

2016-12-01

Although early detection of cancer through screening can prevent cancer deaths, a drawback of screening is overdiagnosis. Overdiagnosis has been much debated in breast cancer screening, but less so in cervical cancer screening. We examined the impact of overdiagnosis by comparing two screening programmes in the Netherlands. We estimated overdiagnosis rates by microsimulation for breast cancer screening and cervical cancer screening, using a cohort of women born in 1982 with lifelong follow-up. Overdiagnosis estimates were made analogous to two definitions formed by the UK 2012 breast screening review. Pre-invasive disease was included in both definitions. Screening prevented 921 cervical cancers (-55%) and 378 cervical cancer deaths (-59%), and 169 (-1.3%) breast cancer cases and 970 breast cancer deaths (-21%). The cervical cancer overdiagnosis rate was 74.8% (including pre-invasive disease). Breast cancer overdiagnosis was estimated at 2.5% (including pre-invasive disease). For women of all ages in breast cancer screening, an excess of 207 diagnoses/100,000 women was found, compared with an excess of 3999 diagnoses/100,000 women in cervical cancer screening. For breast cancer, the frequency of overdiagnosis in screening is relatively low, but consequences are evident. For cervical cancer, the frequency of overdiagnosis in screening is high, because of detection of pre-invasive disease, but the consequences per case are relatively small due to less invasive treatment. This illustrates that it is necessary to present overdiagnosis in relation to disease stage and consequences. © The Author(s) 2016.

Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India

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Kulkarni, Prasad S.; Socquet, Muriel; Jadhav, Suresh S.; Kapre, Subhash V.; LaForce, F. Marc; Poonawalla, Cyrus S.

2015-01-01

Background. In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. Method. From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. Results. SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. Conclusions. The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries. PMID:26553678

Global invasive bacterial vaccine-preventable diseases surveillance--2008-2014.

Science.gov (United States)

Murray, Jillian; Agócs, Mary; Serhan, Fatima; Singh, Simarjit; Deloria-Knoll, Maria; O'Brien, Katherine; Mwenda, Jason M; Mihigo, Richard; Oliveira, Lucia; Teleb, Nadia; Ahmed, Hinda; Wasley, Annemarie; Videbaek, Dovile; Wijesinghe, Pushpa; Thapa, Arun Bhadra; Fox, Kimberly; Paladin, Fem Julia; Hajjeh, Rana; Schwartz, Stephanie; Van Beneden, Chris; Hyde, Terri; Broome, Claire; Cherian, Thomas

2014-12-12

Meningitis and pneumonia are leading causes of morbidity and mortality in children globally infected with Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis, and Haemophilus influenzae causing a large proportion of disease. Vaccines are available to prevent many of the common types of these infections. S. pneumoniae was estimated to have caused 11% of deaths in children aged Organization (WHO) has recommended inclusion of PCV in childhood immunization programs worldwide, especially in countries with high child mortality. As of November 26, 2014, a total of 112 (58%) of all 194 WHO member states and 44 (58%) of the 76 member states ever eligible for support from Gavi, the Vaccine Alliance (Gavi), have introduced PCV. Invasive pneumococcal disease (IPD) surveillance that includes data on serotypes, along with meningitis and pneumonia syndromic surveillance, provides important data to guide decisions to introduce PCV and monitor its impact.

Breath analysis as a potential and non-invasive frontier in disease diagnosis: an overview.

Science.gov (United States)

Pereira, Jorge; Porto-Figueira, Priscilla; Cavaco, Carina; Taunk, Khushman; Rapole, Srikanth; Dhakne, Rahul; Nagarajaram, Hampapathalu; Câmara, José S

2015-01-09

Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Tinevimbo Shiri, DrPhD

2017-01-01

Full Text Available Summary: Background: The full extent to which childhood pneumococcal conjugate vaccines (PCV can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease. Methods: In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016, updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010. Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup. Findings: Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8–10·3 for grouped serotypes contained in the seven-valent PCV (PCV7, and 9·5 years (6·1–16·6 for the grouped six additional serotypes contained in the 13-valent PCV (PCV13 but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23 decreased at similar rates per year in adults aged 19–64 years (relative risk [RR] 0·85, 95% CrI 0·75–0·95 and 65 years and older (0·87, 0·84–0·90. However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13. Interpretation: Population childhood PCV programmes will lead, on average, to substantial protection across the whole population

Serotype distribution of Streptococcus pneumoniae causing invasive disease in the Republic of Ireland.

LENUS (Irish Health Repository)

Vickers, I

2011-05-01

The 7-valent pneumococcal conjugate vaccine (PCV7) was included in the routine infant immunization schedule in Ireland in September 2008. We determined the serotype of 977 S. pneumoniae isolates causing invasive disease between 2000-2002 and 2007-2008, assessed for the presence of the recently described serotype 6C and determined the susceptibility of isolates during 2007-2008 to penicillin and cefotaxime. Serotype 14 was the most common serotype during both periods and 7·7% of isolates previously typed as serotype 6A were serotype 6C. During 2000-2002 and 2007-2008, PCV7 could potentially have prevented 85% and 74% of invasive pneumococcal disease in the target population (i.e. children aged <2 years), respectively. The level of penicillin non-susceptibility was 17% in 2007-2008. Ongoing surveillance of serotypes is required to determine the impact of PCV7 in the Irish population and to assess the potential of new vaccines with expanded valency.

Optimizing Outcomes in Immunocompromised Hosts: Understanding the Role of Immunotherapy in Invasive Fungal Diseases

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Sharada eRavikumar

2015-11-01

Full Text Available A major global concern is the emergence and spread of systemic life –threatening fungal infections in critically ill patients. The increase in invasive fungal infections, caused most commonly by Candida and Aspergillus species, occurs in patients with impaired defenses due to a number of reasons such as underlying disease, the use of chemotherapeutic and immunosuppressive agents, broad-spectrum antibiotics, prosthetic devices and grafts, burns, neutropenia and HIV infection. The high morbidity and mortality associated with these infections is compounded by the limited therapeutic options and the emergence of drug resistant fungi. Hence, creative approaches to bridge the significant gap in antifungal drug development needs to be explored. Here, we review the potential anti-fungal targets for patient-centered therapies and immune-enhancing strategies for the prevention and treatment of invasive fungal diseases.

Development of non-invasive ventilation treatment practice for patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Christensen, Helle M; Titlestad, Ingrid L; Huniche, Lotte

2017-01-01

Objectives: Non-invasive ventilation treatment for patients with acute exacerbation of chronic obstructive pulmonary disease is well documented. Communication with patients during treatment is inhibited because of the mask, the noise from the machine and patient distress. Assessing life expectanc...

The diagnosis and management of pre-invasive breast disease: Problems associated with management of pre-invasive lesions

International Nuclear Information System (INIS)

Purushotham, Anand D

2003-01-01

The treatment of ductal carcinoma in situ (DCIS) involves adequate surgical excision with adjuvant radiotherapy where appropriate. An inadequate excision margin and young age are independent risk factors for local recurrence. Routine surgery to axillary lymph nodes is not recommended in pure DCIS. In localised DCIS, adjuvant radiotherapy is recommended on the basis of tumour size, margin width and pathological subtypes. The role of adjuvant tamoxifen as systemic therapy is controversial. The treatment of atypical ductal/lobular hyperplasia and lobular carcinoma in situ involves surgical excision to exclude coexisting DCIS or invasive disease

Deeply invasive candidiasis.

NARCIS (Netherlands)

Ostrosky-Zeichner, L.; Rex, J.H.; Bennett, J.; Kullberg, B.J.

2002-01-01

The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology. Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease.

Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview

Directory of Open Access Journals (Sweden)

Jorge Pereira

2015-01-01

Full Text Available Currently, a small number of diseases, particularly cardiovascular (CVDs, oncologic (ODs, neurodegenerative (NDDs, chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc. allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

Diagnostic and prognostic value of non-invasive imaging in known or suspected coronary artery disease

International Nuclear Information System (INIS)

Schuijf, J.D.; Poldermans, D.; Shaw, L.J.; Jukema, J.W.; Wall, E.E. van der; Lamb, H.J.; Roos, A. de; Wijns, W.; Bax, J.J.

2006-01-01

The role of non-invasive imaging techniques in the evaluation of patients with suspected or known coronary artery disease (CAD) has increased exponentially over the past decade. The traditionally available imaging modalities, including nuclear imaging, stress echocardiography and magnetic resonance imaging (MRI), have relied on detection of CAD by visualisation of its functional consequences (i.e. ischaemia). However, extensive research is being invested in the development of non-invasive anatomical imaging using computed tomography or MRI to allow detection of (significant) atherosclerosis, eventually at a preclinical stage. In addition to establishing the presence of or excluding CAD, identification of patients at high risk for cardiac events is of paramount importance to determine post-test management, and the majority of non-invasive imaging tests can also be used for this purpose. The aim of this review is to provide an overview of the available non-invasive imaging modalities and their merits for the diagnostic and prognostic work-up in patients with suspected or known CAD. (orig.)

Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality

DEFF Research Database (Denmark)

Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M

2014-01-01

BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or ...

A simultaneous minimally invasive approach to treat a patient with coronary artery disease and metastatic lung cancer.

Science.gov (United States)

Fu, Yuanhao; Zhang, Lufeng; Ji, Ling; Xu, Chenyang

2016-01-01

Concurrent lung cancer and coronary artery disease requiring treatment with percutaneous coronary intervention or coronary artery bypass grafting is not rare. An individualized perioperative anticoagulation regimen and minimal surgical trauma will benefit the patient's postoperative recovery. We successfully treated a 68-year-old female patient with a lesion in the left anterior descending artery and metastatic right lung carcinoma by simultaneous minimally invasive direct coronary artery bypass grafting via a small left thoracotomy and thoracoscopic wedge resection of the lung lesion. She recovered and was discharged on the eighth postoperative day. The patient showed no symptoms of myocardial ischemia postoperatively. Computed tomography scan did not indicate metastatic lesion of lung carcinoma at 1-year follow-up. In conclusion, minimally invasive direct coronary artery bypass grafting combined with thoracoscopic wedge resection is an effective minimally invasive treatment for concurrent lung cancer and coronary artery disease. This technique eliminates the risk of perioperative bleeding and provides satisfactory mid-term follow-up results.

Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: a systematic review.

Science.gov (United States)

Mendes, Luzia; Azevedo, Nuno Filipe; Felino, António; Pinto, Miguel Gonçalves

2015-01-01

Bacterial invasion of the periodontal tissues has been suggested as a relevant step in the etiopathogenesis of periodontal disease. However, its exact importance remains to be defined. The present systematic review assessed the scientific evidence concerning the relationship between the quality or quantity of periodontal microbiota in periodontal tissues and development of periodontal disease. The databases Medline-PubMed, Cochrane-CENTRAL, ISI Web of Knowledge and SCOPUS were searched, up to January 2014. Studies that reported evaluation of periodontal pathogens invasion on human tissues were selected. The screening of 440 title/abstracts elected 26 papers for full-text reading. Twenty three papers were subsequently excluded because of insufficient data or a study protocol not related to the objectives of this systematic review. All included studies were case-control studies that evaluated intracellular or adherent bacteria to epithelial cells from periodontal pockets versus healthy sulci. Study protocols presented heterogeneity regarding case and control definitions and methodological approaches for microbial identification. No consistent significant differences were found related to the presence/absence or proportion of specific periopathogens across the studies, as only one study found statistically significant differences regarding the presence of A. actinomycetemcomitans (p = 0.043), T. forsythia (P periodontal pockets vs. healthy sulci. All studies reported a larger unspecific bacterial load in or on the epithelial cells taken from a diseased site compared to a healthy sulcus. The current available data is of low to moderate quality and inconsistent mainly due to study design, poor reporting and methodological diversity. As so, there is insufficient evidence to support or exclude the invasion by periodontal pathogens as a key step in the etiopathogenesis of periodontal disease. Further research is needed.

Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

Science.gov (United States)

Shi, Bibo; Grimm, Lars J; Mazurowski, Maciej A; Baker, Jay A; Marks, Jeffrey R; King, Lorraine M; Maley, Carlo C; Hwang, E Shelley; Lo, Joseph Y

2018-03-01

The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Adherent-invasive Escherichia coli in inflammatory bowel disease.

Science.gov (United States)

Palmela, Carolina; Chevarin, Caroline; Xu, Zhilu; Torres, Joana; Sevrin, Gwladys; Hirten, Robert; Barnich, Nicolas; Ng, Siew C; Colombel, Jean-Frederic

2018-03-01

Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli , and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn's disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease.

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Elisa Ramos-Sevillano

2016-03-01

Full Text Available Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1 on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium--the amidase LytA--were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1-/- mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1-/- mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease.

Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease.

Directory of Open Access Journals (Sweden)

Melanie Craven

Full Text Available Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn's Disease (CD is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis.We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI; 0.1 mg/mouse, or high dose indomethacin (HDI; 1 mg/mouse. The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype.Moderate to severe ileitis induced by T. gondii (day 8 and HDI caused a consistent shift from >95% gram + Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/-, and reduced dysbiosis in ileitis-resistant CCR2(-/- mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion.Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD.

Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease.

Science.gov (United States)

Craven, Melanie; Egan, Charlotte E; Dowd, Scot E; McDonough, Sean P; Dogan, Belgin; Denkers, Eric Y; Bowman, Dwight; Scherl, Ellen J; Simpson, Kenneth W

2012-01-01

Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn's Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI; 0.1 mg/mouse), or high dose indomethacin (HDI; 1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% gram + Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/-), and reduced dysbiosis in ileitis-resistant CCR2(-/-) mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion. Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD.

A case report of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast.

Science.gov (United States)

Brinkman, David; Misra, Subhasis; Aydin, Nail

2016-01-01

Invasive lobular carcinoma is the second most common type of breast cancer, responsible for 5-15 percent of all cases. Peritoneal carcinomatosis secondary to breast cancer is a rare event, frequently resulting in morbidity and mortality. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast is a very rare event and is not well covered in literature. A 44year old female patient previously diagnosed with stage IV invasive lobular carcinoma of the left breast with widespread systemic metastases and peritoneal carcinomatosis presented with a three week history of right upper quadrant pain trigged by food intake only, greatly diminishing her quality of life. She had spent almost a year in a progression free disease status but was now suffering from debilitating symptomatic gallbladder disease. Despite the extent of her peritoneal carcinomatosis, she elected to undergo a laparoscopic cholecystectomy. We are presenting a rare case of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma. A major concern is tumor load within nearby portal structures. Even though laparoscopic cholecystectomy could be a viable option to treat the condition, it needs to be applied selectively and very cautiously in the respective patient population. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma is an uncommon presentation to surgeons. A diagnostic laparoscopy is the preferred initial evaluation. If deemed feasible, and if the surgeon has the required experience, a laparoscopic cholecystectomy can be undertaken selectively. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine.

Science.gov (United States)

O'Connor, Daniel; Clutterbuck, Elizabeth A; Thompson, Amber J; Snape, Matthew D; Ramasamy, Maheshi N; Kelly, Dominic F; Pollard, Andrew J

2017-01-30

Neisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines. Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination and 7, 21 and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray. Seven days after an initial dose of either vaccine, a gene expression signature characteristic of plasmablasts was detectable. The frequency of newly generated plasma cells (CXCR3 + HLA-DR + ) and the expression of transcripts derived from IGKC and IGHG2 correlated with immunogenicity. Notably, using an independent dataset, the expression of glucosamine (N-acetyl)-6-sulfatase was found to reproducibly correlate with the magnitude of immune response. Transcriptomic and flow cytometric data revealed depletion of switched memory B cells following plain-polysaccharide vaccine. These data describe distinct gene signatures associated with the production of high-avidity antibody and a plain-polysaccharide-specific signature, possibly linked to polysaccharide-induced hyporesponsiveness.

Clonal Distribution of Disease-Associated and Healthy Carrier Isolates of Neisseria meningitidis between 1983 and 2005 in Cuba ▿

Science.gov (United States)

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

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

Science.gov (United States)

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].

Public health action and mass chemoprophylaxis in response to a small meningococcal infection outbreak at a nursery in the West Midlands, England.

Science.gov (United States)

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.

Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: a systematic review

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Mendes, Luzia; Azevedo, Nuno Filipe; Felino, António; Pinto, Miguel Gonçalves

2015-01-01

Bacterial invasion of the periodontal tissues has been suggested as a relevant step in the etiopathogenesis of periodontal disease. However, its exact importance remains to be defined. The present systematic review assessed the scientific evidence concerning the relationship between the quality or quantity of periodontal microbiota in periodontal tissues and development of periodontal disease. The databases Medline-PubMed, Cochrane-CENTRAL, ISI Web of Knowledge and SCOPUS were searched, up to January 2014. Studies that reported evaluation of periodontal pathogens invasion on human tissues were selected. The screening of 440 title/abstracts elected 26 papers for full-text reading. Twenty three papers were subsequently excluded because of insufficient data or a study protocol not related to the objectives of this systematic review. All included studies were case-control studies that evaluated intracellular or adherent bacteria to epithelial cells from periodontal pockets versus healthy sulci. Study protocols presented heterogeneity regarding case and control definitions and methodological approaches for microbial identification. No consistent significant differences were found related to the presence/absence or proportion of specific periopathogens across the studies, as only one study found statistically significant differences regarding the presence of A. actinomycetemcomitans (p = 0.043), T. forsythia (P < 0.001), P. intermedia (P < 0.001), C. ochracea (P < 0.001) and C. rectus (P = 0.003) in epithelial cells from periodontal pockets vs. healthy sulci. All studies reported a larger unspecific bacterial load in or on the epithelial cells taken from a diseased site compared to a healthy sulcus. The current available data is of low to moderate quality and inconsistent mainly due to study design, poor reporting and methodological diversity. As so, there is insufficient evidence to support or exclude the invasion by periodontal pathogens as a key step in the

MICROBIOLOGICAL CHARACTERISATION OF Haemophilus influenzae STRAINS ISOLATED FROM PATIENTS WITH INVASIVE AND RESPIRATORY DISEASES

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Tomislav Kostyanev

2010-01-01

Full Text Available A total of 175 H. influenzae strains were collected between 1994 and 2009 from all aged patient groups. The strains were isolated from patients with invasive and community-acquired respiratory tract infections. All strains were identified according to standard microbiological methods. Serotyping was done by a coagglutination test and by molecular PCR capsular genotyping. Beta-lactamase production was determined by the chromogenic cephalosporin test with nitrocephin as substrate. Most of the isolated H. influenzae strains were from children under 5 years of age (57.7%. Overall, 61 strains belonged to serotype b (34.9% by the means of PCR capsular typing, 1 strain was type f, and 113 isolates (64.6% were non-typeable (non-encapsulated H. influenzae. Among the infants and children with meningitis or other invasive infections, aged 2 month to 5 years, all strains, except one, were serotype b. In respiratory tract infections (pneumonia, otitis media, sinusitis and people with chronic pulmonary diseases - exacerbations of COPD, bronchiectasis, cystic fibrosis the most common - 96.5% were non-typeable strains in both groups children and adults. Overall, the prevalence of beta-lactamase production was 19.4%. But, it was much higher for invasive strains from CSF isolates - 37.7%, 25% in blood samples, and 37.5% in otitis media causative strains. Beta-lactamase production was less frequent in respiratory tract isolates - in sputum 13.3% and in URT samples - 2.3%. The rate of beta-lactamase production in CSF isolates has not changed for the last 10 years.PCR capsular genotyping method has to be performed for all non-b-type strains. The implementation of Hib vaccine in our country will be accompanied by a reduction in invasive diseases caused by H. influenzae type b in children, but it is not useful in preventing infections caused by non-typeable H. influenzae strains.

A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

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Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

2014-09-08

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

Spillover but no spillback of two invasive parasitic copepods from invasive Pacific oysters (

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Goedknegt, M.A.; Schuster, A.-K.; Buschbaum, C.; Gergs, R.; Jung, A.; Luttikhuizen, P.C.; Van der Meer, J.; Troost, K.; Wegner, K.M.; Thieltges, D.W.

2017-01-01

Invasive species can cause indirect effects on native biota by modifying parasite-host interactions and disease occurrence in native species. This study investigated the role of the invasive Pacific oyster (Crassostrea gigas) in potential spillover (co-introduced parasites infect native hosts) and

Neisseria meningitidis Infecting a Prosthetic Knee Joint: A New Case of an Unusual Disease

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Berta Becerril Carral

2017-01-01

Full Text Available Primary meningococcal meningitis is an infrequent but known disease. However, the infection of a prosthetic joint with Neisseria meningitidis is rare. We hereby describe the second case of an arthroplasty infected with Neisseria meningitidis that responded favourably to prosthesis retention with surgical debridement, in combination with antibiotics treatment.

Meningococcal B Vaccination (4CMenB in Infants and Toddlers

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Susanna Esposito

2015-01-01

Full Text Available 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.

Immunology, epidemiology and mathematical modelling towards a better understanding of invasive non-typhoidal Salmonella disease and rational vaccination approaches.

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Mastroeni, Pietro; Rossi, Omar

2016-12-01

Invasive non-typhoidal Salmonella (iNTS) infections cause a high burden of lethal sepsis in young children and HIV patients, often associated with malaria, anaemia, malnutrition and sickle-cell disease. Vaccines against iNTS are urgently needed but none are licensed yet. Areas covered: This review illustrates how immunology, epidemiology and within-host pathogen behaviour affect invasive Salmonella infections and highlights how this knowledge can assist the improvement and choice of vaccines. Expert Commentary: Control of iNTS disease requires approaches that reduce transmission and improve diagnosis and treatment. These are often difficult to implement due to the fragile ecology and economies in endemic countries. Vaccines will be key tools in the fight against iNTS disease. To optimise vaccine design, we need to better define protective antigens and mechanisms of resistance to disease in susceptible populations even in those individuals where innate immunity may be impaired by widespread comorbidities.

Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials

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Siontis, George CM; Mavridis, Dimitris; Greenwood, John P; Coles, Bernadette; Nikolakopoulou, Adriani; Jüni, Peter; Salanti, Georgia

2018-01-01

Abstract Objective To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Design Systematic review and network meta-analysis. Data sources Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Eligibility criteria for selecting studies Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. Data synthesis A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. Results 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with

Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.

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Barnes, Rosemary A; Stocking, Kate; Bowden, Sarah; Poynton, Matthew H; White, P Lewis

2013-09-01

The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Detection of Volatile Compounds Emitted from Nasal Secretions and Serum: Towards Non-Invasive Identification of Diseased Cattle Biomarkers

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Devin L. Maurer

2018-03-01

Full Text Available Non-invasive diagnostics and finding biomarkers of disease in humans have been a very active research area. Some of the analytical technologies used for finding biomarkers of human disease are finding their use in livestock. Non-invasive sample collection from diseased cattle using breath and headspace of fecal samples have been reported. In this work, we explore the use of volatile organic compounds (VOCs emitted from bovine nasal secretions and serum for finding biomarkers for bovine respiratory disease (BRD. One hundred nasal swabs and 100 serum samples (n = 50 for both ‘sick’ and ‘healthy’ were collected at the time of treatment for suspected BRD. Solid-phase microextraction (SPME was used to collect headspace samples that were analyzed using gas chromatography-mass spectrometry (GC-MS. It was possible to separate sick cattle using non-invasive analyses of nasal swabs and also serum samples by analyzing and comparing volatiles emitted from each group of samples. Four volatile compounds were found to be statistically significantly different between ‘sick’ and ‘normal’ cattle nasal swabs samples. Five volatile compounds were found to be significantly different between ‘sick’ and ‘normal’ cattle serum samples, with phenol being the common marker. Future studies are warranted to improve the extraction efficiency targeting VOCs preliminarily identified in this study. These findings bring us closer to the long-term goal of real-time, animal-side detection and separation of sick cattle.

Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease

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Craven, Melanie; Egan, Charlotte E.; Dowd, Scot E.; McDonough, Sean P.; Dogan, Belgin; Denkers, Eric Y.; Bowman, Dwight; Scherl, Ellen J.; Simpson, Kenneth W.

2012-01-01

Background and Aims Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% Gram + Firmicutes to >95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2−/−, and reduced dysbiosis in ileitis-resistant CCR2−/− mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion. Conclusions Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD. PMID:22848538

Use of non-invasive ventilation is increasing in patients admitted with a chronic obstructive pulmonary disease exacerbation

DEFF Research Database (Denmark)

Tøttenborg, Sandra Søgaard; Johnsen, Søren Paaske; Thomsen, Reimar Wernich

2013-01-01

INTRODUCTION: A nationwide chronic obstructive pulmonary disease (COPD) quality improvement programme - DrCOPD - was initiated in Denmark in 2008. We examined subsequent national and regional trends in the use of non-invasive ventilation (NIV) and trends in mortality following NIV and invasive...... the launch of a national COPD quality programme in 2008. However, regional variation remains and no substantial improvements in mortality have been observed. Continued efforts are warranted to ensure appropriate implementation of NIV. FUNDING: The study was supported financially by University of Copenhagen...

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants.

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Baxter, Roger; Keshavan, Pavitra; Welsch, Jo Anne; Han, Linda; Smolenov, Igor

2016-05-03

Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age- and serogroup-specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups.

Progress towards meningitis prevention in the conjugate vaccines era

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Cristina Aparecida Borges Laval

Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013.

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Sadia Shakoor

Full Text Available While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81 of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults. Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52 or CSF specimens (n = 59. Serogroup 18 was the most common serogroup causing meningitis in children <5 years, accounting for 21% of cases (n = 13. The 10-valent pneumococcal conjugate vaccine (PCV 10 or PCV10- related serotypes were found in 61% (n = 47 of childhood (age 0-15 years meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48. Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease.

Timeliness of notification in infectious disease cases.

OpenAIRE

Domínguez, A; Coll, J J; Fuentes, M; Salleras, L

1992-01-01

Records of notification in cases of eight infectious diseases in the "Servei Territorial de Salut Publica" of the Province of Barcelona, Spain, between 1982 and 1986 were reviewed. Time from onset of symptoms to notification, time from notification to completion of data collection, and time from onset to completion of the case investigation were analyzed. For the period from onset to notification, the shortest mean was registered for meningococcal infection (6.31 days) and the longest was for...

Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

DEFF Research Database (Denmark)

Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard

2014-01-01

BACKGROUND: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2......, on susceptibility and disease severity of IPD in previously healthy children aged

Medical Surveillance Monthly Report. Volume 21, Number 7

Science.gov (United States)

2014-07-01

Health Research Center Laboratory–based Meningococcal Disease Surveillance Program, 2006–2014 Michael P. Broderick , PhD S U M M A R Y T A B L E S A N...2006–2014 Michael P. Broderick , PhD F I G U R E . Annual counts of fatal and non-fatal cases of meningococcal disease among active duty service members...1998. Clin Infect Dis. 2002;35(11):1376–1381. 2. Broderick MP, Faix DJ, Hansen CJ, Blair PJ. Trends in meningococcal disease in the United States

IgA1 antibodies specific for outer membrane protein PorA modulate the interaction between Neisseria meningitidis and the epithelium

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Horton, R. E.; Vidarsson, G.; Virji, M.; Williams, N. A.; Heyderman, R. S.

2009-01-01

Despite high carriage rates of Neisseria meningitidis, incidence of meningococcal disease remains low, partially due to development of natural immunity. We have previously demonstrated an inverse relationship between salivary anti-meningococcal IgA and disease incidence, but little is known about

Meningococcal Carriage among College Freshmen in Kashmir, North India- A Single Centre Study

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Nargis K Bali

2017-10-01

Full Text Available Introduction: Data on the community carriage of meningococci in developing countries are sparse. Knowledge about the same would help identify demographic and socio-behavioural risk factors, the need for infection control strategies and the composition of the relevant serogroup for locally effective meningococcal vaccine. Aim: To assess the meningococcal carriage and the major serotypes among fresh college hostellers. Materials and Methods: Charcoal-impregnated nasopharyngeal swabs were collected from 274 consenting fresh college recruits (first year students residing in the college hostel and plated on to Thayer-Martin medium. Oxidase-positive diplococci were taken as presumptive Neisseria species. DNA was extracted from the isolates and Sanger sequencing was performed on the amplified PCR product. Blast analysis of all sequenced samples was performed against the retrieved Neisseria meningitidis sequences from whole NCBI-nr/nt database and within the dataset. Phylogentic analysis was done by Mega-6 professional package comparing published sequences of serogroups against the detected Neisseria meningitidis. Results: Ten (3.6% samples grew oxidase-positive diplococci suggestive of Neisseria. On molecular testing and sequence analysis, 4 samples were found to be N.meningitidis, one (Neisseria spp had close similarity to N.meningitidis and the others included N.perflava (n= 3, N.pharyngis (n=1 and N. flavescens (n=1. N.meningitidis isolates on blast and phylogenetic analysis bore molecular homology to serogroup B. Conclusion: Nasal carriage of N. meningitis (serogroup B was found in about 1.5% (n=4 of the fresh college recruits in the present study. Close proximity amongst the hostellers is likely to result in transmission and such preventive strategies for infection control are desirable. Further, studies of similar kind are mandated to determine the appropriate serogroups required for inclusion in the vaccine.

Primary extramammary invasive Paget’s vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

International Nuclear Information System (INIS)

Tolia, Maria; Tsoukalas, Nikolaos; Sofoudis, Chrisostomos; Giaginis, Constantinos; Spyropoulou, Despoina; Kardamakis, Dimitrios; Kouloulias, Vasileios; Kyrgias, George

2016-01-01

Primary invasive Extramammary Paget’s vulvar disease is a rare tumor that is challenging to control. Wide surgical excision represents the standard treatment approach for Primary invasive Extramammary Paget’s vulvar disease. The goal of the current study was to analyze the appropriate indications of radiotherapy in Primary invasive Extramammary Paget's vulvar disease because they are still controversial. We searched the Cochrane Gynecological Cancer Group Trials Register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE database up to September 2015. Radiotherapy was delivered as a treatment in various settings: i) Radical in 28 cases (range: 60–63 Gy), ii) Adjuvant in 25 cases (range: 39–60 Gy), iii) Salvage in recurrence of 3 patients (63 Gy) and iv) Neoadjuvant in one patient (43.3 Gy). A radiotherapy field that covered the gross tumor site with a 2–5 cm margin for the microscopic disease has been used. Radiotherapy of the inguinal, pelvic or para-aortic lymph node should be considered only for the cases with lymph node metastases within these areas. Radiotherapy alone is an alternative therapeutic approach for patients with extensive inoperable disease or medical contraindications. Definitive radiotherapy can be used in elderly patients and/or with medical contraindications. Adjuvant radiotherapy may be considered in presence of risk factors associated with local recurrence as dermal invasion, lymph node metastasis, close or positive surgical margins, perineal, large tumor diameter, multifocal lesions, extensive disease, coexisting histology of adenocarcinoma or vulvar carcinoma, high Ki-67 expression, adnexal involvement and probably in overexpression of HER-2/neu. Salvage radiotherapy can be given in inoperable loco-regional recurrence and to those who refused additional surgery

Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.

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King, Jill; Pana, Zoi-Dorothea; Lehrnbecher, Thomas; Steinbach, William J; Warris, Adilia

2017-09-01

Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.

Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials.

Science.gov (United States)

Siontis, George Cm; Mavridis, Dimitris; Greenwood, John P; Coles, Bernadette; Nikolakopoulou, Adriani; Jüni, Peter; Salanti, Georgia; Windecker, Stephan

2018-02-21

To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Systematic review and network meta-analysis. Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with suspected stable coronary artery disease, an initial diagnostic strategy of stress echocardiography or

Non-invasive assessment determine the swallowing and respiration dysfunction in early Parkinson's disease.

Science.gov (United States)

Wang, Chin-Man; Shieh, Wann-Yun; Weng, Yi-Hsin; Hsu, Yi-Hsuan; Wu, Yih-Ru

2017-09-01

Dysphagia is common among patients with Parkinson's disease. Swallowing and its coordination with respiration is extremely important to achieve safety swallowing. Different tools have been used to assess this coordination, however the results have been inconsistent. We aimed to investigate this coordination in patients with Parkinson's disease using a non-invasive method. Signals of submental muscle activity, thyroid cartilage excursion, and nasal airflow during swallowing were recorded simultaneously. Five different water boluses were swallowed three times, and the data were recorded and analyzed. Thirty-seven controls and 42 patients with early-stage Parkinson's disease were included. The rates of non-expiratory/expiratory pre- and post-swallowing respiratory phase patterns were higher in the patients than in the controls (P Parkinson's disease, and safety compensation mechanisms were used more than efficiency during swallowing. The results of this study may serve as a baseline for further research into new treatment regimens and to improve the management of swallowing in patients with Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: preliminary data

Science.gov (United States)

Zhu, Zhe; Harowicz, Michael; Zhang, Jun; Saha, Ashirbani; Grimm, Lars J.; Hwang, Shelley; Mazurowski, Maciej A.

2018-02-01

Approximately 25% of patients with ductal carcinoma in situ (DCIS) diagnosed from core needle biopsy are subsequently upstaged to invasive cancer at surgical excision. Identifying patients with occult invasive disease is important as it changes treatment and precludes enrollment in active surveillance for DCIS. In this study, we investigated upstaging of DCIS to invasive disease using deep features. While deep neural networks require large amounts of training data, the available data to predict DCIS upstaging is sparse and thus directly training a neural network is unlikely to be successful. In this work, a pre-trained neural network is used as a feature extractor and a support vector machine (SVM) is trained on the extracted features. We used the dynamic contrast-enhanced (DCE) MRIs of patients at our institution from January 1, 2000, through March 23, 2014 who underwent MRI following a diagnosis of DCIS. Among the 131 DCIS patients, there were 35 patients who were upstaged to invasive cancer. Area under the ROC curve within the 10-fold cross-validation scheme was used for validation of our predictive model. The use of deep features was able to achieve an AUC of 0.68 (95% CI: 0.56-0.78) to predict occult invasive disease. This preliminary work demonstrates the promise of deep features to predict surgical upstaging following a diagnosis of DCIS.

Invasive Species Science Branch: research and management tools for controlling invasive species

Science.gov (United States)

Reed, Robert N.; Walters, Katie D.

2015-01-01

Invasive, nonnative species of plants, animals, and disease organisms adversely affect the ecosystems they enter. Like “biological wildfires,” they can quickly spread and affect nearly all terrestrial and aquatic ecosystems. Invasive species have become one of the greatest environmental challenges of the 21st century in economic, environmental, and human health costs, with an estimated effect in the United States of more than $120 billion per year. Managers of the Department of the Interior and other public and private lands often rank invasive species as their top resource management problem. The Invasive Species Science Branch of the Fort Collins Science Center provides research and technical assistance relating to management concerns for invasive species, including understanding how these species are introduced, identifying areas vulnerable to invasion, forecasting invasions, and developing control methods. To disseminate this information, branch scientists are developing platforms to share invasive species information with DOI cooperators, other agency partners, and the public. From these and other data, branch scientists are constructing models to understand and predict invasive species distributions for more effective management. The branch also has extensive herpetological and population biology expertise that is applied to harmful reptile invaders such as the Brown Treesnake on Guam and Burmese Python in Florida.

Fractional flow reserve derived from coronary CT angiography in stable coronary disease: a new standard in non-invasive testing?

International Nuclear Information System (INIS)

Noergaard, B.L.; Jensen, J.M.; Leipsic, J.

2015-01-01

Fractional flow reserve (FFR) measured during invasive coronary angiography is the gold standard for lesion-specific decisions on coronary revascularization in patients with stable coronary artery disease (CAD). Current guidelines recommend non-invasive functional or anatomic testing as a gatekeeper to the catheterization laboratory. However, the ''holy grail'' in non-invasive testing of CAD is to establish a single test that quantifies both coronary lesion severity and the associated ischemia. Most evidence to date of such a test is based on the addition of computational analysis of FFR to the anatomic information obtained from standard-acquired coronary CTA data sets at rest (FFR CT ). This review summarizes the clinical evidence for the use of FFR CT in stable CAD in context to the diagnostic performance of other non-invasive testing modalities. (orig.)

Neisseria meningitidis RTX protein FrpC induced high levels of serum antibodies during invasive disease: polymorphism of frpC alleles and purification of recombinant FrpC

Czech Academy of Sciences Publication Activity Database

Osička, Radim; Kalmusová, J.; Křížová, P.; Šebo, Peter

2001-01-01

Roč. 69, č. 9 (2001), s. 5509-5519 ISSN 0019-9567 R&D Projects: GA ČR GV310/96/K102; GA MŠk ME 167 Institutional research plan: CEZ:AV0Z5020903 Keywords : Neisseria meningitidis * meningococcal infections Subject RIV: EE - Microbiology, Virology Impact factor: 4.212, year: 2001

Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

Science.gov (United States)

Anderson, Beverley

2018-05-10

Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

DEFF Research Database (Denmark)

Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

2013-01-01

PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

Predicted Strain Coverage of a New Meningococcal Multicomponent Vaccine (4CMenB in Spain: Analysis of the Differences with Other European Countries.

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Raquel Abad

Full Text Available A novel meningococcal multicomponent vaccine, 4CMenB (Bexsero®, has been approved in Europe, Canada, Australia and US. The potential impact of 4CMenB on strain coverage is being estimated by using Meningococcal Antigen Typing System (MATS, an ELISA assay which measures vaccine antigen expression and diversity in each strain. Here we show the genetic characterization and the 4CMenB potential coverage of Spanish invasive strains (collected during one epidemiological year compared to other European countries and discuss the potential reasons for the lower estimate of coverage in Spain.A panel of 300 strains, a representative sample of all serogroup B Neisseria meningitidis notified cases in Spain from 2009 to 2010, was characterized by multilocus sequence typing (MLST and FetA variable region determination. 4CMenB vaccine antigens, PorA, factor H binding protein (fHbp, Neisseria Heparin Binding Antigen (NHBA and Neisserial adhesin A (NadA were molecularly typed by sequencing. PorA coverage was assigned to strain with VR2 = 4. The levels of expression and cross-reactivity of fHbp, NHBA and NadA were analyzed using MATS ELISA.Global estimated strain coverage by MATS was 68.67% (95% CI: 47.77-84.59%, with 51.33%, 15.33% and 2% of strains covered by one, two and three vaccine antigens, respectively. The predicted strain coverage by individual antigens was: 42% NHBA, 36.33% fHbp, 8.33% PorA and 1.33% NadA. Coverage within the most prevalent clonal complexes (cc was 70.37% for cc 269, 30.19% for cc 213 and 95.83% for cc 32.Clonal complexes (cc distribution accounts for variations in strain coverage, so that country-by-country investigations of strain coverage and cc prevalence are important. Because the cc distribution could also vary over time, which in turn could lead to changes in strain coverage, continuous detailed surveillance and monitoring of vaccine antigens expression is needed in those countries where the multicomponent vaccine is introduced

201thallium myocardial scintigraphy. A non-invasive method for diagnosis of ischaemic heart disease

International Nuclear Information System (INIS)

Kyst Madsen, J.; Utne, H.E.

1982-01-01

Myocardial perfusion scintigraphy with the isotope 201 thallium is a new non-invasive technique for the diagnosis of ischaemic heart disease. This article presents the results of scintigraphy in four persons with presumably healthy hearts and 12 with ischaemic heart disease. In addition, some foreign works are reviewed. The method possesses only slightly greater nosographical sensitivity than the exercise ECG alone but can be employed to advantage if the results of the exercise ECG are inconclusive e.g. on account of bundle branch block, digoxin therapy etc. Another, although somewhat more special indication, is employment prior to and after coronary artery by-pass operation with subsequent control of the result. (authors)

Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

Science.gov (United States)

Shi, Bibo; Hou, Rui; Mazurowski, Maciej A.; Grimm, Lars J.; Ren, Yinhao; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

2018-02-01

Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

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.

Science.gov (United States)

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.

Meningokoksepsis diagnosticeret ved realtids-polymerasekædereaktion

DEFF Research Database (Denmark)

Harboe, Zitta B; Howitz, Michael F; Nørgaard, Christina

2008-01-01

Approximately 100 cases of meningococcal disease are reported annually in Denmark; 90% of these cases are confirmed by culture and serological methods. Real-time PCR was introduced in Denmark in 2005 as a diagnostic tool for meningococcal disease. We hereby report the first notified case of menin...

2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan

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Hsiang-Chi Kung

2018-02-01

Full Text Available The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug–drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.

Minimally invasive surgical treatment options for patients with degenerative lumbar spine disease

International Nuclear Information System (INIS)

Durny, P.

2014-01-01

The most common cause of reduced activity in working people is degenerative disc disease and spondylosis of lumbar spine. The variety of clinical findings such as segmental lumbago or severe form of mixed radicular compression syndromes can be occurred. Neurosurgical intervention is indicated in case of failure of conservative treatment and graphical findings correlating with a clinical picture. Large decompressive surgical procedures can destabilize segments previously affected. Recommendations from recent years suggested the functional reconstruction of damaged parts of the vertebrae, intervertebral discs and joints. Continuously improving surgical procedures and instrumentations, intended for operative treatment of lumbar spine degenerative diseases is primarily an effort to improve the properties of implants while minimizing tissue damage during the approach to the target structure. To protect functions of active spine stabilizer and paraspinal muscles is an important factor for the final outcome of the operation. Depend on the nature and extent of the disease the approaches to the spine can be an anterior, lateral and posterior as open surgery or minimally invasive procedures. (author)

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

DEFF Research Database (Denmark)

Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S

2008-01-01

Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children vaccine (PCV7) into the Danish routine...... children vaccination....... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children children

Pathogenesis of invasive candidiasis.

NARCIS (Netherlands)

Veerdonk, F.L. van de; Kullberg, B.J.; Netea, M.G.

2010-01-01

PURPOSE OF REVIEW: Disseminated candidiasis remains a life-threatening disease in the ICU. The development of invasive disease with Candida albicans is dependent on multiple factors, such as colonization and efficient host defense at the mucosa. In the present review, we describe the host defense

Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease.

Science.gov (United States)

Sousa, Adrian; Pérez-Rodríguez, Maria Teresa; Nodar, Andrés; Martínez-Lamas, Lucía; Vasallo, Francisco Jose; Álvarez-Fernández, Maximiliano; Crespo, Manuel

2017-06-22

Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). We present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. A total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0

Homozygosity and risk of childhood death due to invasive bacterial disease

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Williams Thomas N

2009-06-01

Full Text Available Abstract Background Genetic heterozygosity is increasingly being shown to be a key predictor of fitness in natural populations, both through inbreeding depression, inbred individuals having low heterozygosity, and also through chance linkage between a marker and a gene under balancing selection. One important component of fitness that is often highlighted is resistance to parasites and other pathogens. However, the significance of equivalent loci in human populations remains unclear. Consequently, we performed a case-control study of fatal invasive bacterial disease in Kenyan children using a genome-wide screen with microsatellite markers. Methods 148 cases, comprising children aged Results At five markers homozygosity was strongly associated with mortality (odds ratio range 4.7 – 12.2 with evidence of interactions between some markers. Mortality was associated with different non-overlapping marker groups in Gram positive and Gram negative bacterial disease. Homozygosity at susceptibility markers was common (prevalence 19–49% and, with the large effect sizes, this suggests that bacterial disease mortality may be strongly genetically determined. Conclusion Balanced polymorphisms appear to be more widespread in humans than previously appreciated and play a critical role in modulating susceptibility to infectious disease. The effect sizes we report, coupled with the stochasticity of exposure to pathogens suggests that infection and mortality are far from random due to a strong genetic basis.

Imperfect pathogen detection from non-invasive skin swabs biases disease inference

Science.gov (United States)

DiRenzo, Graziella V.; Grant, Evan H. Campbell; Longo, Ana; Che-Castaldo, Christian; Zamudio, Kelly R.; Lips, Karen

2018-01-01

1. Conservation managers rely on accurate estimates of disease parameters, such as pathogen prevalence and infection intensity, to assess disease status of a host population. However, these disease metrics may be biased if low-level infection intensities are missed by sampling methods or laboratory diagnostic tests. These false negatives underestimate pathogen prevalence and overestimate mean infection intensity of infected individuals. 2. Our objectives were two-fold. First, we quantified false negative error rates of Batrachochytrium dendrobatidis on non-invasive skin swabs collected from an amphibian community in El Copé, Panama. We swabbed amphibians twice in sequence, and we used a recently developed hierarchical Bayesian estimator to assess disease status of the population. Second, we developed a novel hierarchical Bayesian model to simultaneously account for imperfect pathogen detection from field sampling and laboratory diagnostic testing. We evaluated the performance of the model using simulations and varying sampling design to quantify the magnitude of bias in estimates of pathogen prevalence and infection intensity. 3. We show that Bd detection probability from skin swabs was related to host infection intensity, where Bd infections information in advance, we advocate that the most cautious approach is to assume all errors are possible and to accommodate them by adjusting sampling designs. The modeling framework presented here improves the accuracy in estimating pathogen prevalence and infection intensity.

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

Directory of Open Access Journals (Sweden)

Hoan Jong Lee

2014-11-01

Conclusions: 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.

Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults

NARCIS (Netherlands)

de Voer, Richarda M.; van der Klis, Fiona R. M.; Engels, Carla W. A. M.; Schepp, Rutger M.; van de Kassteele, Jan; Sanders, Elisabeth A. M.; Rijkers, Ger T.; Berbers, Guy A. M.

2009-01-01

In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n = 21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC

Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

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Kristin Bornstein

2017-02-01

Full Text Available In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis has revealed non-typhoidal Salmonella (NTS to be a major pathogen exhibiting high case fatality (~20%. Where infant vaccination against Haemophilus influenzae type b (Hib and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for

Impact of the invasive parasitic copepod

NARCIS (Netherlands)

Goedknegt, M.A.; Bedolfe; Drent, J.; van der Meer, J.; Thieltges, D.W.

2018-01-01

Invasive species can indirectly affect native species by modifying parasite–host dynamics and disease occurrence. This scenario applies to European coastal waters where the invasive Pacific oyster (Magallana gigas) co-introduced the parasitic copepod Mytilicola orientalis that spills

Direct costs and cost-effectiveness of dual-source computed tomography and invasive coronary angiography in patients with an intermediate pretest likelihood for coronary artery disease.

Science.gov (United States)

Dorenkamp, Marc; Bonaventura, Klaus; Sohns, Christian; Becker, Christoph R; Leber, Alexander W

2012-03-01

The study aims to determine the direct costs and comparative cost-effectiveness of latest-generation dual-source computed tomography (DSCT) and invasive coronary angiography for diagnosing coronary artery disease (CAD) in patients suspected of having this disease. The study was based on a previously elaborated cohort with an intermediate pretest likelihood for CAD and on complementary clinical data. Cost calculations were based on a detailed analysis of direct costs, and generally accepted accounting principles were applied. Based on Bayes' theorem, a mathematical model was used to compare the cost-effectiveness of both diagnostic approaches. Total costs included direct costs, induced costs and costs of complications. Effectiveness was defined as the ability of a diagnostic test to accurately identify a patient with CAD. Direct costs amounted to €98.60 for DSCT and to €317.75 for invasive coronary angiography. Analysis of model calculations indicated that cost-effectiveness grew hyperbolically with increasing prevalence of CAD. Given the prevalence of CAD in the study cohort (24%), DSCT was found to be more cost-effective than invasive coronary angiography (€970 vs €1354 for one patient correctly diagnosed as having CAD). At a disease prevalence of 49%, DSCT and invasive angiography were equally effective with costs of €633. Above a threshold value of disease prevalence of 55%, proceeding directly to invasive coronary angiography was more cost-effective than DSCT. With proper patient selection and consideration of disease prevalence, DSCT coronary angiography is cost-effective for diagnosing CAD in patients with an intermediate pretest likelihood for it. However, the range of eligible patients may be smaller than previously reported.

Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

Energy Technology Data Exchange (ETDEWEB)

Duska, F.; Bradna, P.; Pospisil, M.; Kubicek, J.; Vizda, J.; Kafka, P.; Palicka, V.; Mazurova, Y.

1987-02-01

Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

Energy Technology Data Exchange (ETDEWEB)

Duska, F; Bradna, P; Pospisil, M; Kubicek, J; Vizda, J; Kafka, P; Palicka, V; Mazurova, Y

1987-02-01

Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

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Ana Cristina Cisne Frota

Full Text Available Abstract Objective: HIV-infected individuals (HIVI are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA after a meningococcal C conjugate (MCC vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU, aged 2–18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4 at baseline and at 12–18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02. 85 HIVI (44% had undetectable viral load (UVL. Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12–18 months after immunization (p = 0.14. Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2–766.6; UVL at entry (OR: 2.87, 95% CI: 0.96–8.62 and lower family income (OR: 0.09, 95% CI: 0.01–0.69 were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

International Nuclear Information System (INIS)

Rosenkrantz, Andrew B.; Mussi, Thais C.; Melamed, Jonathan; Taneja, Samir S.; Huang, William C.

2012-01-01

Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

Energy Technology Data Exchange (ETDEWEB)

Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

2012-07-15

Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

[Non-invasive assessment of fatty liver].

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Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

2015-04-05

As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

[Two cases of invasive Haemophilus influenzae type f infection

DEFF Research Database (Denmark)

Nielsen, J.D.; Lind, J.W.; Bruun, B.

2009-01-01

Two cases of invasive Haemophilus influenzae type f infection are presented: a three-week-old boy with meningitis and a 62-year-old woman with arthritis and bacteremia. Since 1993 vaccination against H. influenzae type b (Hib) has been offered to Danish children. The result has been a remarkable...... decrease in invasive Hib disease. However, physicians need to be aware of the existence of non-type b invasive H. influenzae disease Udgivelsesdato: 2009/1/19...

Treatment of intervertebral disc degenerative disease using percutaneous nucleotomy–an overview of less invasive procedures

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Miran Jeromel

2014-04-01

Full Text Available Background: Less invasive treatment methods for intervertebral disc disease and decompression of neural structures as a consequence of contained disc herniation represent an alternative to surgical procedure. Percutaneus nucleotomy uses a percutaneous approach to the intervertebral disc. The article presents the evolution of numerous procedureds in clinical practice.Methods: Percutaneous nucleoplasty is a fluoroscopy-guided procedure which enables controlled and safe entrance into the intervertebral disc. The procedure is performed under strict aseptic conditions, using a local anaesthesia with the patient under analgosedation. Based on the principle of therapeutic intradiscal action, the procedures can be divided into three groups: chemical (chemonucleolysis with chimopapain, alcohol, ozone, mechanical (automated percutaneous lumbar discectomy – APLD, arthroscopic discectomy and thermical methods (laser, radiofrequency ablation, intradiscal electrothermal annuloplasty – IDET, Coblation®.Results: Percutaneous nucleotomy by the majority of the mentioned procedures results in a therapeutic effect (reduction of pain and decompression of neural structures. Fast recovery represents a major advantage of less invasive treatment.Conclusions: Less invasive method (nucleotomy using different procedures represents a successful alternative approach to surgical discectomy. Proper patient selection and safe technique are mandatory in order to achieve a good clinical outcome.

Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats

NARCIS (Netherlands)

Toropainen, Maija; Saarinen, Leena; Vidarsson, Gestur; Käyhty, Helena

2006-01-01

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and

Identifying and treating a life-threatening disease.

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Cole, Beverley

2014-02-01

Meningococcal septicaemia is a life-threatening condition that all nurses working in emergency and urgent care settings are likely to come across during their careers. This article presents, and reflects on, a case study involving a woman with the disease whose signs and symptoms were atypical, and who was not therefore diagnosed with the condition immediately. The author aims to raise awareness among emergency nurses and nurse practitioners of the atypical signs and symptoms of the infection, and its consequences. The article also discusses how referring to patient scenarios can improve practice.

Invasive fungal infections in Colombian patients with systemic lupus erythematosus.

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Santamaría-Alza, Y; Sánchez-Bautista, J; Fajardo-Rivero, J F; Figueroa, C L

2018-06-01

Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality and hospital readmission compared with patients with systemic lupus erythematosus without invasive fungal infection.

The invasive MenC cc103 lineage with penicillin reduced susceptibility persisting in Brazil.

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Fonseca, Érica L; Marin, Michel A; Freitas, Fernanda S; Vitório, Bruna S A; de Araújo, Flávio M G; Camargo, Dhian R A; Coimbra, Roney S; De Filippis, Ivano R; Vicente, Ana Carolina P

2017-09-01

Penicillin is the antibiotic of choice for the treatment of meningococcal infections, and mutations in penA gene are involved with reduced susceptibility (pen I ) emergence to this antibiotic. This study aimed to characterize the penA allelic diversity, their association with pen I phenotype and distribution among prevalent meningococci serogroups in Brazil. The entire penA from 49 invasive strains of distinct serogroups circulating in Brazil for more than two decades were obtained by PCR and sequencing. Additionally, the penA from 22 publicly available complete Neisseria meningitidis genomes from Brazil were included in the study. The allelic diversity was determined and a genetic tree was built using the penA sequence alignment. The penicillin MIC was obtained by the E-Test method. In general, the identified penA alleles correlated with the observed pen I phenotype. The canonical penA1 was the most prevalent allele, however, several altered penA were also identified in strains presenting increased penicillin MICs. It was identified a new penA amino acid position (residue 480) that possibly influence the penicillin MIC in some strains. Interestingly, the altered penA14 was found in pen I invasive MenC cc103 strains spread in Brazil and persisting since 2011, indicating that the biological cost imposed by pen I phenotype can be ameliorated by particular features present in this lineage, which represents an additional public health threat. Copyright © 2017 Elsevier GmbH. All rights reserved.

Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

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Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

2014-10-01

Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management of invasive thymoma at Groote Schuur Hospital, Cape ...

African Journals Online (AJOL)

Fifteen patients (median age 55 years; range 23 - 69 years) with macroscopic invasive thymoma or thymic carcinoma were treated at Groote Schuur Hospital between 1969 and 1988. Stage 3 (macroscopically invasive) disease was present in 12 patients (80%) and stage 4 (metastatic disease) in 3 (20%). Ten of the patients ...

Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010–2014

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Djingarey, Mamoudou H.; Diomandé, Fabien V. K.; Barry, Rodrigue; Kandolo, Denis; Shirehwa, Florence; Lingani, Clement; Novak, Ryan T.; Tevi-Benissan, Carol; Perea, William; Preziosi, Marie-Pierre; LaForce, F. Marc

2015-01-01

Background. A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African “meningitis belt” and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. Methods. With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. Results. Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. Conclusions. The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary. PMID:26553672

The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

International Nuclear Information System (INIS)

Jeffrey, Stefanie S; Pollack, Jonathan R

2003-01-01

Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication

Molecular markers in disease detection and follow-up of patients with non-muscle invasive bladder cancer.

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Maas, Moritz; Walz, Simon; Stühler, Viktoria; Aufderklamm, Stefan; Rausch, Steffen; Bedke, Jens; Stenzl, Arnulf; Todenhöfer, Tilman

2018-05-01

Diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC) is mainly based on endoscopic bladder evaluation and urine cytology. Several assays for determining additional molecular markers (urine-, tissue- or blood-based) have been developed in recent years but have not been included in clinical guidelines so far. Areas covered: This review gives an update on different molecular markers in the urine and evaluates their role in patients with NMIBC in disease detection and surveillance. Moreover, the potential of recent approaches such as DNA methylation assays, multi-panel RNA gene expression assays and cell-free DNA analysis is assessed. Expert commentary: Most studies on various molecular urine markers have mainly focused on a potential replacement of cystoscopy. New developments in high throughput technologies and urine markers may offer further advantages as they may represent a non-invasive approach for molecular characterization of the disease. This opens new options for individualized surveillance strategies and may help to choose the best therapeutic option. The implementation of these technologies in well-designed clinical trials is essential to further promote the use of urine diagnostics in the management of patients with NMIBC.

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

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

2014-01-01

Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diversity of prophage DNA regions of Streptococcus agalactiae clonal lineages from adults and neonates with invasive infectious disease.

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Mazen Salloum

Full Text Available The phylogenetic position and prophage DNA content of the genomes of 142 S. agalactiae (group-B streptococcus, GBS isolates responsible for bacteremia and meningitis in adults and neonates were studied and compared. The distribution of the invasive isolates between the various serotypes, sequence types (STs and clonal complexes (CCs differed significantly between adult and neonatal isolates. Use of the neighbor-net algorithm with the PHI test revealed evidence for recombination in the population studied (PHI, P = 2.01 × 10(-6, and the recombination-mutation ratio (R/M was 6:7. Nevertheless, the estimated R/M ratio differed between CCs. Analysis of the prophage DNA regions of the genomes of the isolates assigned 90% of the isolates to five major prophage DNA groups: A to E. The mean number of prophage DNA fragments amplified per isolate varied from 2.6 for the isolates of prophage DNA group E to 4.0 for the isolates of prophage DNA group C. The isolates from adults and neonates with invasive diseases were distributed differently between the various prophage DNA groups (P < 0.00001. Group C prophage DNA fragments were found in 52% of adult invasive isolates, whereas 74% of neonatal invasive isolates had prophage DNA fragments of groups A and B. Differences in prophage DNA content were also found between serotypes, STs and CCs (P < 0.00001. All the ST-1 and CC1 isolates, mostly of serotype V, belonged to the prophage DNA group C, whereas 84% of the ST-17 and CC17 isolates, all of serotype III, belonged to prophage DNA groups A and B. These data indicate that the transduction mechanisms, i.e., gene transfer from one bacterium to another by a bacteriophage, underlying genetic recombination in S. agalactiae species, are specific to each intraspecies lineage and population of strains responsible for invasive diseases in adults and neonates.

To tilfaelde af invasive infektioner med Haemophilus influenzae type f

DEFF Research Database (Denmark)

Nielsen, Jette Dettmann; Lind, Jens Wentzel; Bruun, Britta

2009-01-01

Two cases of invasive Haemophilus influenzae type f infection are presented: a three-week-old boy with meningitis and a 62-year-old woman with arthritis and bacteremia. Since 1993 vaccination against H. influenzae type b (Hib) has been offered to Danish children. The result has been a remarkable...... decrease in invasive Hib disease. However, physicians need to be aware of the existence of non-type b invasive H. influenzae disease. Udgivelsesdato: 2009-Jan...

To tilfaelde af invasive infektioner med Haemophilus influenzae type f

DEFF Research Database (Denmark)

Nielsen, Jette Dettmann; Lind, Jens; Bruun, Brita

2009-01-01

Two cases of invasive Haemophilus influenzae type f infection are presented: a three-week-old boy with meningitis and a 62-year-old woman with arthritis and bacteremia. Since 1993 vaccination against H. influenzae type b (Hib) has been offered to Danish children. The result has been a remarkable...... decrease in invasive Hib disease. However, physicians need to be aware of the existence of non-type b invasive H. influenzae disease. Udgivelsesdato: 2009-Jan-19...

Population genetics of the Asian tiger mosquito Aedes albopictus, an invasive vector of human diseases

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Goubert, C; Minard, G; Vieira, C; Boulesteix, M

2016-01-01

The Asian tiger mosquito Aedes albopictus is currently one of the most threatening invasive species in the world. Native to Southeast Asia, the species has spread throughout the world in the past 30 years and is now present in every continent but Antarctica. Because it was the main vector of recent Dengue and Chikungunya outbreaks, and because of its competency for numerous other viruses and pathogens such as the Zika virus, A. albopictus stands out as a model species for invasive diseases vector studies. A synthesis of the current knowledge about the genetic diversity of A. albopictus is needed, knowing the interplays between the vector, the pathogens, the environment and their epidemiological consequences. Such resources are also valuable for assessing the role of genetic diversity in the invasive success. We review here the large but sometimes dispersed literature about the population genetics of A. albopictus. We first debate about the experimental design of these studies and present an up-to-date assessment of the available molecular markers. We then summarize the main genetic characteristics of natural populations and synthesize the available data regarding the worldwide structuring of the vector. Finally, we pinpoint the gaps that remain to be addressed and suggest possible research directions. PMID:27273325

A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

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Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

2008-12-01

The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

Minimally invasive surgical treatment for temporomandibular joint in patients with various rheumatic diseases

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A. Yu. Drobyshev

2017-01-01

Full Text Available Temporomandibular joint (TMJ involvement occurs in patients with different rheumatic diseases (RDs. Pain, limitation of mouth opening can lead to significant problems in both oral hygiene and when eating. Conservative treatments for TMJ lesions are not always effective. Objective: to evaluate the efficiency of minimally invasive surgical interventions (TMJ arthrocentesis and arthroscopy in patients with RDs. Patients and methods. The investigation enrolled 64 patients with different RDs (43 with rheumatoid arthritis, 11 with psoriatic arthritis, 8 with systemic lupus erythematosus, and 2 with ankylosing spondylitis who were divided into three groups in relation to the severity of TMJ involvement in accordance with the Wilkes classification. All the patients underwent TMJ magnetic resonance imaging at baseline and 6 months after treatment. Also at baseline, 14 days, and 1, 6, and 12 months after surgery, the investigators assessed TMJ pain intensity by visual analogue scale and the parameters of mandibular movements. Patients with Wilkes stages IV and V TMJ involvement underwent arthroscopic intervention into the TMJ and those with III stage received TMJ arthrocentesis with arthrolavage. Results and discussion. After surgical treatment, all the groups were noted to have a significant decrease in TMJ pain intensity compared with the baseline level; moreover, the severity of TMJ pain most significantly decreased on day 7 after surgery. Later on, positive changes remained within subsequent follow-up months. There were data similar in the higher degree of mouth opening. The results of surgical treatment in patients with Wilkes stage V TMJ involvement were worse than in those with stages III and IV. Conclusion. Minimally invasive TMJ surgery in patients with RDs is effective and associated with the low frequency of postoperative complications and exacerbations of RDs. The efficiency of minimally invasive TMJ surgery is higher in patients with the

N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease.

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Jernberg, Tomas; Lindahl, Bertil; Siegbahn, Agneta; Andren, Bertil; Frostfeldt, Gunnar; Lagerqvist, Bo; Stridsberg, Mats; Venge, Per; Wallentin, Lars

2003-12-03

We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy. Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome. Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI. Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy. N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.

Minimally Invasive Transforaminal Lumbar Interbody Fusion and Unilateral Fixation for Degenerative Lumbar Disease.

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Wang, Hui-Wang; Hu, Yong-Cheng; Wu, Zhan-Yong; Wu, Hua-Rong; Wu, Chun-Fu; Zhang, Lian-Suo; Xu, Wei-Kun; Fan, Hui-Long; Cai, Jin-Sheng; Ma, Jian-Qing

2017-08-01

To evaluate the clinical effect of the minimally invasive transforaminal lumbar interbody fusion combined with posterolateral fusion and unilateral fixation using a tubular retractor in the management of degenerative lumbar disease. A retrospective analysis was conducted to analyze the clinical outcome of 58 degenerative lumbar disease patients who were treated with minimally invasive transforaminal lumbar interbody fusion combined with posterolateral fusion and unilateral fixation during December 2012 to January 2015. The spine was unilaterally approached through a 3.0-cm skin incision centered on the disc space, located 2.5 cm lateral to the midline, and the multifidus muscles and longissimus dorsi were stripped off. After transforaminal lumbar interbody fusion and posterolateral fusion the unilateral pedicle screw fixation was performed. The visual analogue scale (VAS) for back and leg pain, the Oswestry disability index (ODI), and the MacNab score were applied to evaluate clinical effects. The operation time, peri-operative bleeding, postoperative time in bed, hospitalization costs, and the change in the intervertebral height were analyzed. Radiological fusion based on the Bridwell grading system was also assessed at the last follow-up. The quality of life of the patients before and after the operation was assessed using the short form-36 scale (SF-36). Fifty-eight operations were successfully performed, and no nerve root injury or dural tear occurred. The average operation time was 138 ± 33 min, intraoperative blood loss was 126 ± 50 mL, the duration from surgery to getting out of bed was 46 ± 8 h, and hospitalization cost was 1.6 ± 0.2 ten thousand yuan. All of the 58 patients were followed up for 7-31 months, with an average of 14.6 months. The postoperative VAS scores and ODI score were significantly improved compared with preoperative data (P degenerative lumbar disease, and the short-term clinical outcome is satisfactory

Invasive versus Non Invasive Methods Applied to Mummy Research: Will This Controversy Ever Be Solved?

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Day, Jasmine; Bianucci, Raffaella

2015-01-01

Advances in the application of non invasive techniques to mummified remains have shed new light on past diseases. The virtual inspection of a corpse, which has almost completely replaced classical autopsy, has proven to be important especially when dealing with valuable museum specimens. In spite of some very rewarding results, there are still many open questions. Non invasive techniques provide information on hard and soft tissue pathologies and allow information to be gleaned concerning mummification practices (e.g., ancient Egyptian artificial mummification). Nevertheless, there are other fields of mummy studies in which the results provided by non invasive techniques are not always self-explanatory. Reliance exclusively upon virtual diagnoses can sometimes lead to inconclusive and misleading interpretations. On the other hand, several types of investigation (e.g., histology, paleomicrobiology, and biochemistry), although minimally invasive, require direct contact with the bodies and, for this reason, are often avoided, particularly by museum curators. Here we present an overview of the non invasive and invasive techniques currently used in mummy studies and propose an approach that might solve these conflicts. PMID:26345295

Assessment of non-invasive models for liver fibrosis in chronic hepatitis B virus related liver disease patients in resource limited settings.

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Shrivastava, Rakesh; Sen, Sourav; Banerji, Debabrata; Praharaj, Ashok K; Chopra, Gurvinder Singh; Gill, Satyajit Singh

2013-01-01

A total of 350 million individuals are affected by chronic hepatitis B virus infection world-wide. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. A number of non-invasive models have been studied world-wide. The aim of this study is to assess the utility of non-invasive mathematical models of liver fibrosis in chronic hepatitis B (CHB). Indian patients in a resource limited setting using routinely performed non-invasive laboratory investigations. A cross-sectional study carried out at a tertiary care center. A total of 52 consecutive chronic liver disease patients who underwent percutaneous liver biopsy and 25 healthy controls were enrolled in the study. Routine laboratory investigations included serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamyl transpeptidase (GGT), total bilirubin, total cholesterol, prothrombin time and platelet count. Three non-invasive models for namely aspartate aminotransferase to platelet ratio index (APRI), Fibrosis 4 (FIB-4) and Forn's index were calculated. Outcomes were compared for the assessment of best predictor of fibrosis by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each index. Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value value of all 3 indices were significantly higher in patients group as compare with the controls (P model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant fibrosis. Thus, these two non-invasive models for predicting of liver fibrosis, namely APRI and FIB-4, can be utilized in combination as screening tools in monitoring of CHB patients, especially in resource limiting settings.

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

Directory of Open Access Journals (Sweden)

David J. Dowling

2016-12-01

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

Host Physiologic Changes Induced by Influenza A Virus Lead to Staphylococcus aureus Biofilm Dispersion and Transition from Asymptomatic Colonization to Invasive Disease

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Ryan M. Reddinger

2016-08-01

Full Text Available Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease. S. aureus is a major source of severe secondary bacterial pneumonia after influenza A virus infection, which causes widespread morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is well established, the mechanisms behind the transition from asymptomatic colonization to invasive staphylococcal disease following viral infection remains unknown. In this report, we have shown that S. aureus biofilms, grown on an upper respiratory epithelial substratum, disperse in response to host physiologic changes related to viral infection, such as febrile range temperatures, exogenous ATP, norepinephrine, and increased glucose. Mice that were colonized with S. aureus and subsequently exposed to these physiologic stimuli or influenza A virus coinfection developed pronounced pneumonia. This study provides novel insight into the transition from colonization to invasive disease, providing a better understanding of the events involved in the pathogenesis of secondary staphylococcal pneumonia.

Mechanisms of cellular invasion by intracellular parasites.

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Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

2014-04-01

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales.

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Yoon Hong Choi

Full Text Available England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7 with its 13-valent equivalent (PCV13, partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether.A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13.Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether.Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.

Medical and surgical treatment of idiopathic granulomatous lobular mastitis: a benign inflammatory disease mimicking invasive carcinoma.

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Gurleyik, Gunay; Aktekin, Ali; Aker, Fugen; Karagulle, Hikmet; Saglamc, Abdullah

2012-03-01

Idiopathic granulomatous lobular mastitis (IGLM) is a rare chronic inflammatory disease of the breast with obscure etiology that mimics invasive carcinoma both clinically and radiologically. The treatment of IGLM remains controversial. The aim of proper management is to use a combination of medical and surgical treatment of this benign condition to achieve a good cosmetic result and low recurrence rate. A retrospective analysis of 19 patients with IGLM is performed based on the findings of clinical, radiological, and pathological examinations. The results of two treatments are presented: medical treatment with oral corticosteroids, and consecutive surgical excision after a follow-up period of 20 months (range, 6-75 months). The majority of patients treated in this paper were young (mean, 34 years) parous women with a history of hormonal medication use. The main clinical finding is large, irregular, and painful mass. Hypoechoic lobulated, irregular tubular or oval shaped masses had been imaged by ultrasound. Mammographic findings were an ill-defined mass, enlarged axillary lymph nodes, asymmetric density, and architectural distortion. Diagnoses of IGLM had been established by cytological or histological examination. Symptoms subside and inflammatory changes regressed with medical treatment. The remaining lesions were excised by consecutive breast conserving surgery. The disease recurred in one patient during the follow-up period. IGLM is an inflammatory breast disease found in young women who present with a large painful irregular mass, which mimics carcinoma, as a physical change. Breast imaging modalities are not helpful to differentiate IGLM from invasive cancer. The correct diagnosis is established by cytological or histological examination. Medical treatment with corticosteroids provides significant regression of the inflammatory disease, allowing more conservative surgery. Consecutive surgical excision of the remaining lesions with good cosmetic results

Invasion of Porphyromonas gingivalis strains into vascular cells and tissue

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Ingar Olsen

2015-08-01

Full Text Available Porphyromonas gingivalis is considered a major pathogen in adult periodontitis and is also associated with multiple systemic diseases, for example, cardiovascular diseases. One of its most important virulence factors is invasion of host cells. The invasion process includes attachment, entry/internalization, trafficking, persistence, and exit. The present review discusses these processes related to P. gingivalis in cardiovascular cells and tissue. Although most P. gingivalis strains invade, the invasion capacity of strains and the mechanisms of invasion including intracellular trafficking among them differ. This is consistent with the fact that there are significant differences in the pathogenicity of P. gingivalis strains. P. gingivalis invasion mechanisms are also dependent on types of host cells. Although much is known about the invasion process of P. gingivalis, we still have little knowledge of its exit mechanisms. Nevertheless, it is intriguing that P. gingivalis can remain viable in human cardiovascular cells and atherosclerotic plaque and later exit and re-enter previously uninfected host cells.

Validation of non-invasive haemodynamic methods in patients with liver disease

DEFF Research Database (Denmark)

Brittain, Jane M; Busk, Troels M; Møller, Søren

2018-01-01

Patients with advanced cirrhosis often present a hyperdynamic circulation characterized by a decrease in systolic and diastolic blood pressure (SBP and DBP), and an increase in heart rate (HR) and cardiac output (CO). Accurate assessment of the altered circulation can be performed invasively......; however, due to the disadvantages of this approach, non-invasive methods are warranted. The purpose of this study was to compare continuous non-invasive measurements of haemodynamic variables by the Finometer and the Task Force Monitor with simultaneous invasive measurements. In 25 patients with cirrhosis......, respectively; and CO: 0·1 ± 1·6 and -1·0 ± 2·0 L min(-1) , respectively. The study demonstrates that the overall performances of the Finometer and the Task Force Monitor in estimating absolute values of SBP, DBP, HR and CO in patients with cirrhosis are not equivalent to the gold standard, but may have...

Meningococcal Meningitis

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... Iraq Nigeria Somalia South Sudan Syrian Arab Republic Yemen All emergencies » Latest » By country By disease Disease ... conditions in Africa in areas with limited health infrastructure and resources, ceftriaxone is the drug of choice. \\ ...

Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

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Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

2017-01-11

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Role of non-invasive ventilation in difficult-to-wean children with acute neuromuscular disease.

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Reddy, V G; Nair, M P; Bataclan, F

2004-05-01

Weaning from mechanical ventilation in children could be time-consuming and on many occasions, leads to reintubation with its associate complications. We report two children with acute neuromuscular disease, in whom bi-level positive airway pressure (BiPAP) as a mode of non-invasive ventilation was successfully used to wean the child from ventilators and prevented the need for tracheostomy. Despite the limited number of studies published in the literature suggesting BiPAP as a mode of weaning from mechanical ventilation, the technique when applied correctly seems to be safe and effective in weaning and avoiding tracheostomy.

Cancer invasion and the microenvironment: plasticity and reciprocity.

NARCIS (Netherlands)

Friedl, P.H.A.; Alexander, S.

2011-01-01

Cancer invasion is a cell- and tissue-driven process for which the physical, cellular, and molecular determinants adapt and react throughout the progression of the disease. Cancer invasion is initiated and maintained by signaling pathways that control cytoskeletal dynamics in tumor cells and the

[Invasive yeast infections in neutropenic patients].

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Ruiz Camps, Isabel; Jarque, Isidro

2016-01-01

Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques.

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Ward, Erin P; Shiavazzi, Daniele; Sood, Divya; Marsden, Allison; Lane, John; Owens, Erik; Barleben, Andrew

2017-01-01

Currently, the gold standard diagnostic examination for significant aortoiliac lesions is angiography. Fractional flow reserve (FFR) has a growing body of literature in coronary artery disease as a minimally invasive diagnostic procedure. Improvements in numerical hemodynamics have allowed for an accurate and minimally invasive approach to estimating FFR, utilizing cross-sectional imaging. We aim to demonstrate a similar approach to aortoiliac occlusive disease (AIOD). A retrospective review evaluated 7 patients with claudication and cross-sectional imaging showing AIOD. FFR was subsequently measured during conventional angiogram with pull-back pressures in a retrograde fashion. To estimate computed tomography (CT) FFR, CT angiography (CTA) image data were analyzed using the SimVascular software suite to create a computational fluid dynamics model of the aortoiliac system. Inlet flow conditions were derived based on cardiac output, while 3-element Windkessel outlet boundary conditions were optimized to match the expected systolic and diastolic pressures, with outlet resistance distributed based on Murray's law. The data were evaluated with a Student's t-test and receiver operating characteristic curve. All patients had evidence of AIOD on CT and FFR was successfully measured during angiography. The modeled data were found to have high sensitivity and specificity between the measured and CT FFR (P = 0.986, area under the curve = 1). The average difference between the measured and calculated FFRs was 0.136, with a range from 0.03 to 0.30. CT FFR successfully identified aortoiliac lesions with significant pressure drops that were identified with angiographically measured FFR. CT FFR has the potential to provide a minimally invasive approach to identify flow-limiting stenosis for AIOD. Copyright © 2016 Elsevier Inc. All rights reserved.

[Biological factors influencing infectious diseases transmitted by invasive species of mosquitoes].

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Boštíková, Vanda; Pasdiorová, Markéta; Marek, Jan; Prášil, Petr; Salavec, Miloslav; Sleha, Radek; Střtítecká, Hana; Blažek, Pavel; Hanovcová, Irena; Šošovičková, Renáta; Špliňo, Milan; Smetana, Jan; Chlíbek, Roman; Hytych, Václav; Kuča, Kamil; Boštík, Pavel

2016-06-01

Studies focused on arbovirus diseases transmitted by invasive species of mosquitoes have become increasingly significant in recent years, due to the fact that these vectors have successfully migrated to Europe and become established in the region. Mosquitoes, represented by more than 3 200 species, occur naturally worldwide, except in Antarctica. They feed on the blood of warm-blooded animals and by this route, they are capable of transmitting dangerous diseases. Some species can travel a distance of 10 km per night and can fly continuously for up to 4 hours at a speed of 1-2 km/h. Most species are active at night, in the evening or morning. It usually takes a mosquito female about 50 seconds to penetrate the skin of mammals and the subsequent blood meal usually takes about 2.5 minutes. Mosquitoes live for several weeks or months, depending on the environmental conditions. The VectorNet project is a European network of information exchange and sharing of data relating to the geographical distribution of arthropod vectors and transmission of infectious agents between human populations and animals. It aims at the development of strategic plans and vaccination policies which are the main tasks of this time, as well as the development and application of new disinfectants to control vector populations.

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

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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

A Cluster of Paediatric Invasive Group A Streptococcal and Chicken Pox Infections

LENUS (Irish Health Repository)

Ó Maoldomhnaigh, C

2018-03-01

Group A streptococcus (GAS) causes a variety of acute clinical syndromes from pharyngitis and scarlet fever commonly seen in primary care to more severe life-threatening invasive disease. Invasive GAS, categorised into three groups - necrotising fasciitis, streptococcal toxic shock syndrome and sepsis with or without an identifiable source of infection- is a notifiable disease to the Health Protection Surveillance Centre (HPSC)1. Laboratory criteria for a confirmed case require isolation of GAS from a normally sterile site. The HPSC previously reported a marked increase in the incidence of invasive GAS infections from 1.65\\/100,000 population in 2011 to 3.65\\/100,000 in 20132. The increased incidence was notable also for a 300% increase in the proportion of invasive GAS cases in children. After a slight decrease in incidence in 20153 (2.3\\/100000), we noted a cluster of invasive GAS cases referred to the paediatric infectious disease (PID) department of Children’s University Hospital (CUH), Temple Street, in 2016. We sought to further characterise this cluster of paediatric invasive GAS infections.

Invasive Group A streptococcal disease in Ireland, 2004 to 2010.

LENUS (Irish Health Repository)

Martin, J

2011-01-01

Invasive group A streptococcal infections (iGAS) are a major clinical and public health challenge. iGAS is a notifiable disease in Ireland since 2004. The aim of this paper is to describe the epidemiology of iGAS in Ireland for the first time over the seven-year period from 2004 to 2010. The Irish national electronic infectious disease reporting system was used by laboratories to enter the source of iGAS isolates, and by departments of public health to enter clinical and epidemiological details. We extracted and analysed data from 1 January 2004 to 31 December 2010. Over the study period, 400 iGAS cases were notified. The annual incidence of iGAS doubled, from 0.8 per 100,000 population in 2004 to 1.6 in 2008, and then remained the same in 2009 and 2010. The reported average annual incidence rates were highest among children up to five years of age (2.3\\/100,000) and adults aged over 60 years (3.2\\/100,000). The most common risk factors associated with iGAS were skin lesions or wounds. Of the 174 people for whom clinical syndrome information was available, 28 (16%) cases presented with streptococcal toxic shock syndrome and 19 (11%) with necrotising fasciitis. Of the 141 cases for whom seven-day outcomes were recorded, 11 people died with iGAS identified as the main cause of death (seven-day case fatality rate 8%). The notification rate of iGAS in Ireland was lower than that reported in the United Kingdom, Nordic countries and North America but higher than southern and eastern European countries. The reasons for lower notification rates in Ireland compared with other countries may be due to a real difference in incidence, possibly due to prescribing practices, or due to artefacts resulting from the specific Irish case definition and\\/or low reporting in the early stages of a new surveillance system. iGAS disease remains an uncommon but potentially severe disease in Ireland. Ongoing surveillance is required in order to undertake appropriate control measures and