scholarly journals A Case of Fulminant Meningococcemia: It Is All in the Complement

2017 ◽  
Vol 2017 ◽  
pp. 1-3 ◽  
Author(s):  
Kellie L. Hawkins ◽  
Mariah Hoffman ◽  
Sonia Okuyama ◽  
Sarah E. Rowan
Keyword(s):  
Monoclonal Antibody ◽  
Risk Factor ◽  
Antibiotic Prophylaxis ◽  
Neisseria Meningitidis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Complement Deficiency ◽  
Biologic Agent ◽  
Meningococcal Infection ◽  
Increased Risk ◽  
Life Threatening

Eculizumab is a novel monoclonal antibody that inhibits complement-mediated hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Complement deficiency is a well-known risk factor for meningococcal infection. We describe a case of a young patient with PNH treated with eculizumab who presented with a life-threatening case of nongroupable meningococcemia. As this new biologic agent becomes more widely prescribed, providers should be aware of the increased risk of meningococcemia. In addition to vaccination, providers may consider the use of oral penicillin for antibiotic prophylaxis against Neisseria meningitidis in these cases of functional complement deficiency.

#92: What Is the Optimal Management of Patients Immunosuppressed with the Anti-compliment Monoclonal Antibody, Eculizumab? A Case Report and Review

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S12-S12
Author(s):  
I Tinoco ◽  
A Jarrell ◽  
L Correa ◽  
J Bissler ◽  
J DeVincenzo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Renal Failure ◽  
Antibiotic Prophylaxis ◽  
Neisseria Meningitidis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Neisseria Species ◽  
E Coli ◽  
Increased Risk ◽  
Prescribing Information ◽  
Rabbit Complement

Abstract Background Patients with deficiencies of terminal components of complement are at hundreds to thousands fold increased risk of severe and fatal Neisseria spp. infections compared with the general population. Eculizumab is a newly approved monoclonal antibody C5 complement inhibitor. It is indicated for the treatment of atypical hemolytic uremic syndrome (atypical HUS), myasthenia gravis, and paroxysmal nocturnal hemoglobinuria. Because of the complement-depleting effect of Eculizumab dosing (Soliris®, Alexion Pharmaceuticals, Munich, Germany), patients are immunosuppressed for specific infectious pathogens (including Neisseria species) against which protection partially relies on normal complement activity. Because Eculizumab treatment is associated with a dramatically increased risk of Neisseria species. infections, recommendations for Neisseria meningitidis vaccination and antibiotic prophylaxis are contained in Eculizumab prescribing information. However, the most appropriate prevention of infections after Eculizumab has yet to be determined. Methods Case report and literature review. Results A previously healthy 7-year-old male was diagnosed with atypical HUS which included renal failure progressing to dialysis, persistent thrombocytopenia, hemolytic anemia, and hemoglobinuria. Stool cultures and a stool multiplex PCR panel did not detect Shiga-like producing E. coli nor E. coli O157/H7. Eculizumab dosing was therefore planned and Infectious Diseases consultation was obtained for appropriate preventions. The FDA Prescribing Information recommends Neisseria meningitidis vaccination before starting Eculizumab or, if immediate Eculizumab is necessary, to use antibiotic prophylaxis until 2 weeks after vaccination. The accepted protective titer after meningococcal vaccination is population based and uses the serum bactericidal assay (SBA). An antibody titer of >1:4 (human compliment) or 1:8 (rabbit complement) is considered protective. However, this “gold standard” assay incorporates the use of exogenous human or rabbit complement. The protective SBA titers in subjects with terminal complement component deficiencies may not be properly assessed using these same SBA titer protective thresholds. Furthermore, serious meningococcal infections have occurred after appropriate vaccination in patients receiving chronic Eculizumab treatments (ie for paroxysmal nocturnal hemoglobinuria). Finally, SBA protective levels after single Neisseria meningitidis vaccination have not been achieved in majorities of patients with renal failure receiving dialysis and or transplant immunosuppression. Conclusions The current Eculizumab prescribing information recommendations for vaccination and antimicrobial prophylaxis may be inadequate to prevent serious Neisseria infections. Repeated Neisseria meningitidis vaccination and extended antibiotic prophylaxis may afford better protection in patients chronically dosed with Eculizumab.

scholarly journals Anatomical Asplenia in Cat Eye Syndrome:An Expansion of the Disease Spectrum

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
DeepakBabu Chellapandian ◽  
Adele Schneider
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Neisseria Meningitidis ◽  
Bacterial Infections ◽  
Type B ◽  
Disease Spectrum ◽  
Cat Eye Syndrome ◽  
Increased Risk ◽  
Life Threatening ◽  
Penicillin Prophylaxis

We report a patient with Cat eye syndrome (CES) associated with anatomical asplenia. To the best of our knowledge, there have been no prior reports of this association. Screening for asplenia in CES is potentially important, as asplenia places patients at increased risk for life-threatening bacterial infections. Hence patients with CES without a spleen may require the same routine precautions as any other asplenic patients, with penicillin prophylaxis and immunizations to protect against encapsulated organisms such asStreptococcus pneumoniae, Haemophilus influenzaetype b, andNeisseria meningitidis.

scholarly journals Immunization with the Recombinant PorB Outer Membrane Protein Induces a Bactericidal Immune Response against Neisseria meningitidis

2002 ◽  
Vol 70 (8) ◽  
pp. 4028-4034 ◽  
Author(s):  
J. Claire Wright ◽  
Jeannette N. Williams ◽  
Myron Christodoulides ◽  
John E. Heckels
Keyword(s):  
Recombinant Protein ◽  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Lipid A ◽  
Meningococcal Infection ◽  
Native Protein ◽  
Monophosphoryl Lipid A ◽  
Porin Protein ◽  
Life Threatening ◽  
Porin Proteins

ABSTRACT Infections with Neisseria meningitidis are characterized by life-threatening meningitis and septicemia. The meningococcal porin proteins from serogroup B meningococci have been identified as candidates for inclusion in vaccines to prevent such infections. In this study, we investigated the vaccine potential of the PorB porin protein free of other meningococcal components. The porB gene from a strain of Neisseria meningitidis expressing the class 3 outer membrane porin protein (PorB3) was cloned into the pRSETB vector, and the protein was expressed at high levels in a heterologous host Escherichia coli. The recombinant protein was purified to homogeneity by affinity chromatography and used for immunization after incorporation into liposomes and into micelles composed either of zwitterionic detergent or nondetergent sulfobetaine. The immunogenicity of these preparations was compared to recombinant PorB protein adsorbed to Al(OH)3 adjuvant as a control. Although sera raised against the protein adsorbed to Al(OH)3 reacted with the purified recombinant protein, sera raised against liposomes and micelles showed greater activity with native protein, as measured by enzyme immunoassay with outer membranes and by whole-cell immunofluorescence. Reactivity with native protein was considerably enhanced by incorporation of the adjuvant monophosphoryl lipid A into the liposome or micelle preparations. Recognition of the native protein was in a serotype-specific manner and was associated with the ability of the antisera to promote high levels of serotype-specific complement-mediated killing of meningococci. These results demonstrate that the PorB protein should be considered as a component of a vaccine designed to prevent serogroup B meningococcal infection.

scholarly journals Eculizumab impairs Neisseria meningitidis serogroup B killing in whole blood despite 4CMenB vaccination of PNH patients

2020 ◽  
Vol 4 (15) ◽  
pp. 3615-3620 ◽  
Author(s):  
Jeroen D. Langereis ◽  
Bryan van den Broek ◽  
Sjoerd Franssen ◽  
Irma Joosten ◽  
Nicole M. A. Blijlevens ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Whole Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Treatment Success ◽  
Membrane Attack Complex ◽  
Meningococcal Infections ◽  
Major Drawback ◽  
Bacterial Surface ◽  
Life Threatening ◽  
Increased Susceptibility

Abstract Complement C5 inhibitor eculizumab has a great impact on the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). However, this treatment success has a major drawback: a substantially increased susceptibility for life-threatening Neisseria meningitidis infections. Therefore, N meningitidis vaccination is strongly advised before initiating complement C5–blocking therapy. In this study, we show that the multicomponent N meningitidis serogroup B (4CMenB) vaccination of PNH patients treated with eculizumab results in a significant increase in anti–N meningitidis serogroup B (MenB) plasma immunoglobulin G (IgG) levels. Anti-MenB IgG was able to bind to the bacterial surface and initiate complement activation; however, inhibition of the membrane attack complex formation completely blocked whole blood–mediated killing of MenB. This would suggest that, despite 4CMenB vaccination, PNH patients taking C5 inhibitors are not sufficiently protected against MenB infection, which is in line with the fact that vaccinated PNH patients still experience meningococcal infections.

Bacterial Vaccines for Splenectomized Patients

1988 ◽  
Vol 22 (3) ◽  
pp. 192-197 ◽  
Author(s):  
Kondjeni T. Kafidi ◽  
John C. Rotschafer
Keyword(s):  
Streptococcus Pneumoniae ◽  
Adverse Effects ◽  
Neisseria Meningitidis ◽  
Antibody Production ◽  
Pathogenic Bacteria ◽  
Risk Groups ◽  
The Body ◽  
Increased Risk ◽  
Life Threatening ◽  
Encapsulated Bacteria

The spleen is an important organ in the defense of the body against pathogenic bacteria. Major functions of the spleen include antibody production and mechanical filtration of blood. Anatomically or functionally asplenic individuals are at increased risk of fulminant infection by encapsulated bacteria, particularly Streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningitidis. Polysaccharide vaccines are available against some strains of these pathogenic bacteria. More data are required to define specific age and risk groups. A search for better and more immunogenic vaccines, which may prove effective in a wider variety of patients, is currently under way. Although the current vaccines are not always effective and future revaccination may increase the incidence of adverse effects, most asplenic persons should receive the currently available vaccines to minimize their risk of life-threatening infection.

scholarly journals Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Pusem Patir ◽  
Yakup Isik ◽  
Yigit Turk ◽  
Mehmet Can Ugur ◽  
Cengiz Ceylan ◽  
...  
Keyword(s):  
Necrotizing Fasciitis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Flow Cytometric Analysis ◽  
Purulent Discharge ◽  
Klebsiella Pneumonia ◽  
Tissue Destruction ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Superficial Skin ◽  
Life Threatening

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive, and life-threatening hematopoietic stem cell disorder characterized by complement-mediated intravascular hemolysis and a prothrombotic state. Patients with PNH might have slightly increased risk of infections due to complement-associated defects subsequent to CD59 deficiency. Here, we report a rare case of a 65-year-old male patient with necrotic ulcers on both legs, where the recognition of pancytopenia and microthrombi led to the diagnosis of PNH based on FLAER (FLuorescent AERolysin) flow cytometric analysis. He was subsequently started on eculizumab therapy, with starting and maintenance doses set as per drug labelling. Progression of the patient’s leg ulcers during follow-up, with fulminant tissue destruction, purulent discharge, and necrotic patches, led to a later diagnosis of necrotizing fasciitis due toPseudomonas aeruginosaandKlebsiella pneumoniainfection. Courses of broad-spectrum antibiotics, surgical debridement, and superficial skin grafting were applied with successful effect during ongoing eculizumab therapy. This case highlights the point that it is important to maintain treatment of underlying disorders such as PNH in the presence of life-threatening infections like NF.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

2020 ◽  
Vol 26 (43) ◽  
pp. 5617-5627
Author(s):  
Mirjana Stojković ◽  
Miloš Žarković
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiac Electrophysiology ◽  
Vascular System ◽  
Density Lipoprotein ◽  
Thyroid Stimulating Hormone ◽  
Normal Limits ◽  
Developing Heart ◽  
Treatment Indications ◽  
Increased Risk

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

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