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Muscle & Nerve Jul 2019Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN;...
INTRODUCTION
Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.
METHODS
Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.
RESULTS
The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).
DISCUSSION
These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.
Topics: Activities of Daily Living; Adult; Angioedema; Antibodies, Monoclonal, Humanized; Aspergillosis; Complement Inactivating Agents; Disease Progression; Female; Heart Diseases; Humans; Injection Site Reaction; Longitudinal Studies; Male; Meningococcal Infections; Meningococcal Vaccines; Middle Aged; Muscle Strength; Myasthenia Gravis; Quality of Life; Treatment Outcome
PubMed: 30767274
DOI: 10.1002/mus.26447 -
The Journal of Infection Apr 2016Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British...
Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.
Topics: Adult; Critical Care; Humans; Meningitis, Bacterial; Meningococcal Infections; Neisseria meningitidis; Sepsis; Spinal Puncture; United Kingdom
PubMed: 26845731
DOI: 10.1016/j.jinf.2016.01.007 -
Journal of Clinical Microbiology Nov 2022Neisseria meningitidis is a common commensal bacterium found in the respiratory tract, but it can also cause severe, invasive disease. Vaccines have been employed which... (Review)
Review
Neisseria meningitidis is a common commensal bacterium found in the respiratory tract, but it can also cause severe, invasive disease. Vaccines have been employed which have been successful in helping to prevent invasive disease caused by encapsulated N. meningitidis from the A, C, W, Y, and B serogroups. Currently, nonencapsulated N. meningitidis groups are more common commensals in the population than in the prevaccine era. One emerging nonencapsulated group of bacteria is the U.S. N. meningitidis urethritis clade (US_NmUC), which can cause meningococcal urethritis in men. US_NmUC has unique genotypic and phenotypic features that may increase its fitness in the male urethra. It is diagnostically challenging to identify and distinguish meningococcal urethritis from Neisseria gonorrhoeae, as the clinical presentation and microbiological findings are overlapping. In this review, the history of meningococcal urethritis, emergence of US_NmUC, laboratory diagnosis, and clinical treatment are all explored.
Topics: Male; Humans; Urethritis; Neisseria meningitidis; Neisseria gonorrhoeae; Serogroup; Urethra; Meningococcal Infections
PubMed: 35969045
DOI: 10.1128/jcm.00575-22 -
MMWR. Recommendations and Reports :... Sep 2020This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United...
This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk.In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16-23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.
Topics: Adolescent; Adult; Advisory Committees; Centers for Disease Control and Prevention, U.S.; Child; Child, Preschool; Humans; Immunization Schedule; Infant; Meningococcal Infections; Meningococcal Vaccines; Middle Aged; United States; Vaccines, Conjugate; Young Adult
PubMed: 33417592
DOI: 10.15585/mmwr.rr6909a1 -
Human Genetics Jun 2020Neisseria meningitidis is a leading cause of bacterial septicaemia and meningitis worldwide. Meningococcal disease is rare but can be life threatening with a tendency to... (Review)
Review
Neisseria meningitidis is a leading cause of bacterial septicaemia and meningitis worldwide. Meningococcal disease is rare but can be life threatening with a tendency to affect children. Many studies have investigated the role of human genetics in predisposition to N. meningitidis infection. These have identified both rare single-gene mutations as well as more common polymorphisms associated with meningococcal disease susceptibility and severity. These findings provide clues to the pathogenesis of N. meningitidis, the basis of host susceptibility to infection and to the aetiology of severe disease. From the multiple discoveries of monogenic complement deficiencies to the associations of complement factor H and complement factor H-related three polymorphisms to meningococcal disease, the complement pathway is highlighted as being central to the genetic control of meningococcal disease. This review aims to summarise the current understanding of the host genetic basis of meningococcal disease with respect to the different stages of meningococcal infection.
Topics: Complement Factor H; Genetic Predisposition to Disease; Human Genetics; Humans; Meningococcal Infections; Neisseria meningitidis; Polymorphism, Genetic; Virulence
PubMed: 32067109
DOI: 10.1007/s00439-020-02128-4 -
The Journal of Adolescent Health :... Aug 2016Meningococcal disease is a life-threatening infection that may progress rapidly, even after appropriate treatment has commenced. Early suspicion of the diagnosis is... (Review)
Review
Meningococcal disease is a life-threatening infection that may progress rapidly, even after appropriate treatment has commenced. Early suspicion of the diagnosis is vital so that parenteral antibiotic treatment can be administered as soon as possible to reduce the complications of infection. The outcome of meningococcal disease is critically dependent on prompt recognition of two important complications: shock and raised intracranial pressure. Rapid recognition of disease and of these complications, together with appropriate management is crucial to the outcome of affected patients. This article summarizes the clinical features of invasive meningococcal disease, diagnostic tools, treatment modalities, and common post-infection sequelae.
Topics: Anti-Bacterial Agents; Early Diagnosis; Emergency Treatment; Humans; Meningococcal Infections; Neisseria meningitidis; Tomography, X-Ray Computed
PubMed: 27449146
DOI: 10.1016/j.jadohealth.2016.04.013 -
Epidemiology and Infection Oct 2016The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with recognized expertise in meningococcal disease including... (Review)
Review
The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with recognized expertise in meningococcal disease including microbiology, immunology, epidemiology, public health and vaccinology. The GMI was established to promote the global prevention of meningococcal disease through education, research and international cooperation. The GMI held its second summit meeting in 2013 to discuss the different aspects of existing meningococcal immunization programmes and surveillance systems. Laboratory confirmation and characterization were identified as essential for informing evidence-based vaccine implementation decisions. The relative merits of different confirmatory methodologies and their applications in different resource settings were a key component of the discussions. This paper summarizes the salient issues discussed, with special emphasis on the recommendations made and any deficiencies that were identified.
Topics: Guidelines as Topic; Humans; Meningococcal Infections; Public Health
PubMed: 27357022
DOI: 10.1017/S0950268816001308 -
The Journal of Adolescent Health :... Aug 2016
Topics: Cost of Illness; Humans; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Serogroup
PubMed: 27449144
DOI: 10.1016/j.jadohealth.2016.06.002 -
Comptes Rendus Biologies Jul 2021Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Since...
Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Since the first description of the epidemic nature of the illness at the dawn of the nineteenth century, the scientific knowledge of meningococcal infection has increased greatly. Major advances have been made in the management of the disease with the advent of antimicrobial therapy and the implementation of meningococcal vaccines. More recently, an extensive knowledge has been accumulated on meningococcal interaction with its human host, revealing key processes involved in disease progression and new promising therapeutic approaches.
Topics: Anti-Bacterial Agents; Humans; Meningococcal Infections; Neisseria meningitidis; Purpura Fulminans
PubMed: 34213851
DOI: 10.5802/crbiol.56 -
Cold Spring Harbor Perspectives in... Jun 2013Neisseria meningitidis is responsible for two major diseases: cerebrospinal meningitis and/or septicemia. The latter can lead to a purpura fulminans, an often-fatal... (Review)
Review
Neisseria meningitidis is responsible for two major diseases: cerebrospinal meningitis and/or septicemia. The latter can lead to a purpura fulminans, an often-fatal condition owing to the associated septic shock. These two clinical aspects of the meningococcal infection are consequences of a tight interaction of meningococci with host endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of a microbiological synapse. A low level of bacteremia is likely to favor the colonization of brain vessels, leading to bacterial meningitis, whereas the colonization of a large number of vessels by a high number of bacteria is responsible for one of the most severe forms of septic shock observed.
Topics: Bacteremia; Bacterial Adhesion; Bacterial Load; Blood-Brain Barrier; Brain; Cortactin; Endothelial Cells; Fimbriae, Bacterial; Host-Pathogen Interactions; Humans; Meningococcal Infections; Neisseria meningitidis; Phosphorylation; Purpura Fulminans; Receptors, Adrenergic, beta-2
PubMed: 23732856
DOI: 10.1101/cshperspect.a012393