scholarly journals Evidence for Multi-Organ Infection During Experimental Meningococcal Sepsis due to ST-11 Isolates in Human Transferrin-Transgenic Mice

2020 ◽  
Vol 8 (10) ◽  
pp. 1456
Author(s):  
Michael Levy ◽  
Myriam Aouiti Trabelsi ◽  
Muhamed-Kheir Taha
Keyword(s):  
Transgenic Mice ◽  
Organ Failure ◽  
Meningococcal Disease ◽  
Dynamic Imaging ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Human Transferrin ◽  
Multi Organ Failure ◽  
Invasive Infections ◽  
Organ Infection

The description of invasive meningococcal disease that is provoked by Neisseria meningitidis (Nm) is frequently restricted to meningitis. However, a wide panel of clinical presentations can be encountered including severe forms with intense inflammatory reaction leading to multi-organ failure. Several human factors are involved in the development of invasive infections such as transferrin, factor H or CEACAM1. In this study, we used an experimental meningococcal infection in transgenic mice expressing the human transferrin to show multi-organ infection. Mice were infected by an intraperitoneal injection of bacterial suspension (1.5 × 107 colony-forming unit/mouse) of a bioluminescent serogroup C strain belonging to the clonal complex ST-11. Dynamic imaging and histological analysis were performed. The results showed invasion of tissues by Nm with bacteria observed, outside blood vessels, in the kidneys, the heart and the brain as well as skin involvement. These data further support the systemic aspect of invasive meningococcal disease with involvement of several organs including skin as in humans. Thus, our model can be used to study severe forms of meningococcal invasive infections with multi-organ failure.

scholarly journals Doença Meningocócica Invasiva: Aplicação do Base Excess and Platelets Score numa Unidade de Cuidados Intensivos Pediátricos Portuguesa

2015 ◽  
Vol 28 (3) ◽  
pp. 342
Author(s):  
Luis Martins ◽  
Patrícia Mação ◽  
Carla Pinto ◽  
Teresa Dionísio ◽  
Andrea Dias ◽  
...  
Keyword(s):  
Organ Failure ◽  
Meningococcal Disease ◽  
Base Excess ◽  
Invasive Meningococcal Disease ◽  
Meningococcal Infection ◽  
Related Factors ◽  
Mortality And Morbidity ◽  
Multi Organ Failure ◽  
Risk Of Mortality ◽  
Excess Base

<strong>Introduction:</strong> Meningococcal infection has a high mortality and morbidity. Recently a new prognostic scoring system was developed for paediatric invasive meningococcal disease, based on platelet count and base excess – base excess and platelets score. The main objective of this study was to evaluate the accuracy of base excess and platelets score to predict mortality in children admitted to intensive care due to invasive meningococcal disease.<br /><strong>Material and Methods:</strong> Observational study, with retrospective data collection, during a 13.5 years period (01/2000 to 06/2013). Mortality by invasive meningococcal disease and related factors (organ dysfunction and multi-organ failure) were analysed. The base excess and platelets score was calculated retrospectively, to evaluate its accuracy in predicting mortality and compared with Paediatric Risk of Mortality and Paediatric Index of Mortality2.<br /><strong>Results:</strong> Were admitted 76 children with invasive meningococcal disease. The most frequent type of dysfunction was cardiovascular (92%), followed by hematologic (55%). Of the total, 47 patients (62%) had criteria for multi-organ failure. The global mortality was 16%. Neurologic and renal dysfunction showed the strongest association with mortality, adjusted odds ratio 315 (26 - 3 804) and 155 (20 - 1 299).<br />After application of receiver operating characteristic curves, Base Excess and Platelets score had an area under curve of 0.81, Paediatric Index of Mortality2 of 0.91 and Paediatric Risk of Mortality of 0.96.<br /><strong>Discussion: </strong>The Base Excess and Platelets score showed good accuracy, although not as high as Paediatric Risk of Mortality or<br />Paediatric Index of Mortality2.<br /><strong>Conclusions:</strong> The Base Excess and Platelets score may be useful tool in invasive meningococcal disease because is highly sensitive and specific and is objectively measurable and readily available at presentation.

Changing epidemiology of invasive meningococcal disease in Australia 1994–2016

2017 ◽  
Vol 38 (4) ◽  
pp. 184
Author(s):  
Helen V Smith ◽  
Amy V Jennison
Keyword(s):  
Meningococcal Disease ◽  
Age Groups ◽  
Case Fatality ◽  
Antimicrobial Treatment ◽  
Invasive Meningococcal Disease ◽  
Public Health Issue ◽  
Vaccination Programs ◽  
Invasive Infections ◽  
Low Incidence

Invasive meningococcal disease (IMD) has a relatively low incidence in Australia, however remains a serious public health issue, with a case fatality rate of approximately 10% despite antimicrobial treatment. IMD is particularly seen in young children, but can affect all age groups. The disease has non-specific early symptoms, rapid clinical progression mainly manifesting as septicaemia and/or meningitis, and has the potential for long term sequelae in the survivors, including skin scarring, amputation, deafness and seizures. There are 13 serogroups, although most invasive infections worldwide are caused by serogroups A, B, C, W, and Y, with some recent outbreaks in Africa caused by serogroup X. The prevalent circulating serogroups can undergo dynamic shifts, generating dramatic changes in IMD epidemiology. Such serogroup shifts have important ramifications for vaccination programs and constant surveillance is crucial.

scholarly journals Factor H binding protein (fHbp)-mediated differential complement resistance of a serogroup C Neisseria meningitidis isolate from cerebrospinal fluid of a patient with invasive meningococcal disease

2021 ◽  
Vol 3 (9) ◽  
Author(s):  
Alessandra Facchetti ◽  
Jun X. Wheeler ◽  
Caroline Vipond ◽  
Gail Whiting ◽  
Hayley Lavender ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Close Contact ◽  
Binding Protein ◽  
Integral Membrane Protein ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Content Type ◽  
Type Iv ◽  
Complement Resistance

During an outbreak of invasive meningococcal disease (IMD) at the University of Southampton, UK, in 1997, two Neisseria meningitidis serogroup C isolates were retrieved from a student (‘Case’), who died of IMD, and a close contact (‘Carrier’) who, after mouth-to-mouth resuscitation on the deceased, did not contract the disease. Genomic comparison of the isolates demonstrated extensive nucleotide sequence identity, with differences identified in eight genes. Here, comparative proteomics was used to measure differential protein expression between the isolates and investigate whether the differences contributed to the clinical outcomes. A total of six proteins were differentially expressed: four proteins (methylcitrate synthase, PrpC; hypothetical integral membrane protein, Imp; fructose-1,6-bisphosphate aldolase, Fba; aldehyde dehydrogenase A, AldA) were upregulated in the Case isolate, while one protein (Type IV pilus-associated protein, PilC2) was downregulated. Peptides for factor H binding protein (fHbp), a major virulence factor and antigenic protein, were only detected in the Case, with a single base deletion (ΔT366) in the Carrier fHbp causing lack of its expression. Expression of fHbp resulted in an increased resistance of the Case isolate to complement-mediated killing in serum. Complementation of fHbp expression in the Carrier increased its serum resistance by approximately 8-fold. Moreover, a higher serum bactericidal antibody titre was seen for the Case isolate when using sera from mice immunized with Bexsero (GlaxoSmithKline), a vaccine containing fHbp as an antigenic component. This study highlights the role of fHbp in the differential complement resistance of the Case and the Carrier isolates. Expression of fHbp in the Case resulted in its increased survival in serum, possibly leading to active proliferation of the bacteria in blood and death of the student through IMD. Moreover, enhanced killing of the Case isolate by sera raised against an fHbp-containing vaccine, Bexsero, underlines the role and importance of fHbp in infection and immunity.

scholarly journals Does Binding of Complement Factor H to the Meningococcal Vaccine Antigen, Factor H Binding Protein, Decrease Protective Serum Antibody Responses?

2013 ◽  
Vol 20 (8) ◽  
pp. 1099-1107 ◽  
Author(s):  
Dan M. Granoff ◽  
Sanjay Ram ◽  
Peter T. Beernink
Keyword(s):  
Transgenic Mice ◽  
Meningococcal Disease ◽  
Binding Protein ◽  
Factor H ◽  
Antibody Responses ◽  
Vaccine Antigen ◽  
Single Amino Acid ◽  
Complement Factor ◽  
Meningococcal Vaccine ◽  
Bactericidal Antibody

ABSTRACTFactor H binding protein (fHbp) is a principal antigen in a multicomponent meningococcal vaccine recently licensed in Europe for prevention of serogroup B diseases. The protein recruits the complement downregulator, factor H (fH), to the bacterial surface, which enables the organism to resist complement-mediated bacteriolysis. Binding is specific for human fH. In preclinical studies, mice and rabbits immunized with fHbp vaccines developed serum bactericidal antibody responses, which in humans predict protection against developing meningococcal disease. These studies, however, were in animals whose fH did not bind to the vaccine antigen. Here we review the immunogenicity of fHbp vaccines in human fH transgenic mice. The data suggest that animals with high serum human fH concentrations have impaired protective antibody responses. Further, mutant fHbp vaccines with single amino acid substitutions that decrease fH binding are superior immunogens, possibly by unmasking epitopes in the fH binding site that are important for eliciting serum bactericidal antibody responses. Humans immunized with fHbp vaccines develop serum bactericidal antibody, but achieving broad coverage in infants required incorporation of additional antigens, including outer membrane vesicles, which increased rates of fever and local reactions at the injection site. The experimental results in transgenic mice predict that fHbp immunogenicity can be improved in humans by using mutant fHbp vaccines with decreased fH binding. These results have important public health implications for developing improved fHbp vaccines for control of serogroup B meningococcal disease and for development of vaccines against other microbes that bind host molecules.

scholarly journals Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Neisseria meningitidis Strains and Their Predicted Coverage by the 4CMenB Vaccine

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Raymond S. W. Tsang ◽  
Dennis K. S. Law ◽  
Rosita De Paola ◽  
Maria Giuliani ◽  
Maria Stella ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Effective Control ◽  
Atlantic Region ◽  
Content Type ◽  
Laboratory Surveillance ◽  
4Cmenb Vaccine

ABSTRACT The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.

scholarly journals Doença Invasiva Meningocócica em Cuidados Intensivos Pediátricos

2014 ◽  
Vol 27 (3) ◽  
pp. 291 ◽  
Author(s):  
Patrícia Mação ◽  
Gustavo Januário ◽  
Sofia Ferreira ◽  
Andrea Dias ◽  
Teresa Dionísio ◽  
...  
Keyword(s):  
Intensive Care ◽  
Organ Failure ◽  
Meningococcal Disease ◽  
Multiple Organ ◽  
Invasive Meningococcal Disease ◽  
Prognostic Scores ◽  
Meningococcal Infection ◽  
Meningococcal Infections ◽  
Mortality And Morbidity ◽  
Secondary Transport

<strong>Introduction:</strong> Meningococcal infection has a high mortality and morbidity in children. Aggressive initial shock approach, early referral, secondary transport and vaccination are potential factors with impact in reducing its mortality. Objectives were to characterize children admitted to intensive care due to invasive meningococcal disease, to evaluate their prognostic scores and mortality.<br /><strong>Material and Methods:</strong> Observational study, with retrospective data collection. Two periods were created according to the year of admission (A: 2000-2005 and B: 2006-2011). Prognostic parameters, organ failure and mortality rates were compared in these groups.<br /><strong>Results:</strong> 70 children were admitted with invasive meningococcal disease. When compared with other causes of admission, a decrease in the number of admissions due to invasive meningococcal disease was observed (period A: 3.4%; period B: 1.5%; p = 0.001). The presence of meningitis was 41% in period A and 29% in period B (p = 0.461). Rapidly progressive purpura occurred in 78% in period A and 50% in period B (p = 0.032). Children from period A had multi-organ failure (80%), disseminated intravascular coagulation (76%) and coma (22%) more frequently than children from period B (29%, 29%, 0%; p &lt; 0.05). Mortality was 26% in period A and 0% in period B (p = 0.006) and standardized mortality by PRISM was 1.3 and 0 in period A and B respectively.<br /><strong>Discussion:</strong> The decrease in the number of admissions due to invasive meningococcal disease can be explained by the introduction of anti-meningococcal C vaccine in 2006. Mortality decline can be possibly explained by an improvement in the initial patient stabilization and to secondary transport.<br /><strong>Conclusion:</strong> A decrease in the number of admissions due to invasive meningococcal disease and in mortality was observed.<br /><strong>Keywords:</strong> Child; Infant; Intensive Care Units, Pediatric; Meningococcal Infections; Multiple Organ Failure; Mortality; Portugal; Sepsis.

scholarly journals Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120757 ◽  
Author(s):  
Declan T. Bradley ◽  
Thomas W. Bourke ◽  
Derek J. Fairley ◽  
Raymond Borrow ◽  
Michael D. Shields ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Complement System ◽  
Meningococcal Disease ◽  
Binding Protein ◽  
Factor H ◽  
Invasive Meningococcal Disease

scholarly journals Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Margherita Bodini ◽  
Alessandro Brozzi ◽  
Maria Giuliani ◽  
Hanna Nohynek ◽  
Anni Vainio ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Vaccine Coverage ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Heparin Binding ◽  
Protein Variant ◽  
Content Type ◽  
Typing System

ABSTRACT Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a significant cause of morbidity and mortality worldwide. In Finland, the incidence rate of IMD is low, with meningococcal serogroup B (MenB) accounting for around one-third of IMD cases annually. The aim of this study was to investigate the genetic variability of invasive MenB isolates collected in Finland between 2010 and 2017 (n = 81), including the genes encoding the 4-component MenB vaccine (4CMenB; Bexsero; GSK) antigens and their promoters, and to evaluate the 4CMenB potential coverage. Whole-genome sequencing was performed. The meningococcal antigen typing system (MATS) was used to characterize MenB isolates and predict the potential coverage of 4CMenB. MATS was complemented by genetic MATS (gMATS) through association of antigen genotyping and phenotypic MATS results. Multilocus sequence typing revealed predominance of the ST-41/44 clonal complex among which sequence type (ST)-303 was the most common and was predicted to be covered by 4CMenB. Of the 4 major vaccine antigens, the factor H-binding protein variant 1, neisserial heparin binding antigen peptide 2, and the PorA P1.4 antigen were predominant, whereas Neisseria adhesin A was present in only 4% of the 81 isolates. MATS and gMATS 4CMenB strain coverage predictions were 78% and 86%, respectively, in a subpanel of 60 isolates collected during 2010 to 2014, with a gMATS prediction of 84% for all 81 isolates. The results suggest that 4CMenB could reduce the burden of IMD in Finland and that gMATS could be applied to monitor vaccine strain coverage and predict vaccine effectiveness. IMPORTANCE 4CMenB is a 4-component vaccine used against invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B (MenB). We investigated the genetic variability of MenB in Finland and evaluated 4CMenB strain coverage by 2 different methods: MATS (meningococcal antigen typing system) and gMATS (genetic MATS). In a set of MenB isolates, 78% (MATS) and 86% (gMATS) were predicted as covered by 4CMenB, suggesting that use of 4CMenB would help reduce IMD incidence in Finland. MATS has been used in 13 countries worldwide, generating information on phenotypic characteristics that could infer protection by 4CMenB. Based on these data and genetic information, gMATS coverage predictions can be made. gMATS predicts coverage consistent with MATS for about 94% of tested strains. Unlike MATS, gMATS does not require live isolates, thus allowing the analysis also of noncultivable strains, making the coverage predictions more accurate. Therefore, gMATS can replace MATS to assess 4CMenB coverage, including in regions with no prior MATS data.

Thirty-eight-negative-kinase-1 is a major mediator of trauma-induced intestinal injury and multi-organ failure

2018 ◽  
Vol 56 (08) ◽  
pp. e205-e206
Author(s):  
M Armacki ◽  
AK Trugenberger ◽  
A Ellwanger ◽  
T Eiseler ◽  
L Bettac ◽  
...  
Keyword(s):  
Organ Failure ◽  
Intestinal Injury ◽  
Multi Organ Failure ◽  
Major Mediator
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