1) The document discusses new complement inhibitor drugs and their implications for clinical practice and vaccination policy. It reviews complement activation pathways and deficiencies.
2) Patients receiving complement inhibitor treatments like eculizumab are at higher risk for invasive meningococcal disease due to vaccine failures or non-vaccine serogroup infections. One case study showed IMD from a vaccine-targeted but penicillin-resistant strain in a patient on eculizumab.
3) The document recommends vaccination against meningococcal serogroups A, C, W, and Y for those with complement deficiencies from inherited or acquired causes like treatment. It also suggests continuing antibiotic prophylaxis and planning for self-treatment rescue antibiotics
Novartis satellite breakfast session at the Meningitis Research Foundation 2013 conference, Meningitis & Septicaemia in Children & Adults presented by Emeritus Professor Richard Moxon, Dr Jamie Findlow and Dr Simon Nadel
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What next for prevention of pneumococcal disease in light of serotype replacement? Is there a pathway to licensure for novel pneumococcal vaccines?
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Panel discussion moderated by Prof Paul Heath at Meningitis Research Foundation's 2013 Conference, Meningitis and Septicaemia in Children and Adults
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Dr Marie-Pierre Preziosi's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults http://www.meningitis.org/conference2013
Prospects for GBS prevention - current candidates & removing barriers to licensure of a GBS vaccine for pregnant women globally
https://www.meningitis.org/mrf-conference-2017
What next for prevention of pneumococcal disease in light of serotype replacement? Is there a pathway to licensure for novel pneumococcal vaccines?
https://www.meningitis.org/mrf-conference-2017
Panel discussion moderated by Prof Paul Heath at Meningitis Research Foundation's 2013 Conference, Meningitis and Septicaemia in Children and Adults
Panellists: Prof Adam Finn, University of Bristol, Dr Simon Nadel, Prof Robert Read, Dr Matthew Snape and Dr Caroline Trotter
Dr Marie-Pierre Preziosi's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults http://www.meningitis.org/conference2013
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Dr Muhamed-Kheir Taha @ MRF's Meningitis and Septicaemia 2019
1. The new generation of complement
inhibitors and implications for
clinical practice and vaccination
policy
Muhamed-Kheir TAHA MD, PhD
Institut Pasteur
Invasive Bacterial Infections
London MRF Meeting
06/11/2019
2. Activation of the complement
- Humoral innate
immunity system
- Acute-phase
proteins
-19 plasma and at
least 9 membrane
proteins
Harris et al., Molecular Immunology 102 (2018) 89–119
4. Harris et al., Molecular Immunology 102 (2018) 89–119
Pipeline for anti-complement drugs in the
kidney, eye and vasculature
Half-life of ravulizumab is 4 times longer than that of eculizumab
(Lee et al., Blood, 2016)
5. Compstatin
Complement
Inhibition (inhibition
of C3b deposition) on
PNH RBC impact
on both pathways
Complement
Activation on
PNH RBC
Lysis of PNH RBC
- Insertion of C5b-9 MAC
(intravascular hemolysis)
- Opsonization with C3b
(extravascular hemolysis)
No Complement
activation
CD55
(C3b)
CD59
(MAC)
No lysis
Eculizumab
Complement
Inhibition (C5 inhibition)
on PNH RBC
Lysis of PNH RBC is still occurring
Opsonization with C3b
(extravascular hemolysis)
Complement inhibition and hemolysis in PNH
6. Risk groups for IMD
Medical reasons
- Close contacts of patients with IMD;
- Subjects with a terminal complement deficiency or who are
receiving anti-C5 treatment (and other future anti-complement
treatment)
- Subjects with other complement deficiencies (properdin Factor D)
- Subjects with anatomical or functional asplenia;
- Subjects who received a hematopoietic stem cell transplantation
- HIV
- Association with viral infection (flu)
Occupational/societal reasons
Travellers, pilgrims, mass gathering events, military, laboratory staff working
on meningococci, MSM, Students
Epidemic Situations
7. Complement and IMD
Inherited and drug induced complement deficiencies.
- 13% of IMD revealed complement deficiencies in South Africa
(Owen et al., S Afr Med 2012).
- One third of group Y IMD revealed complement deficiency France
(Le Bastard et al., Pathol Biol, 1989 ).
- 7/22 (32%) patients with NG IMD had complement deficiency or
abnormal complement testing results (McNamara et al.,, Open
Forum Infect Dis 6, 2019).
- Among 160 patients with complete TPD; 56 patients (39%) showed
confirmed IMD (France 1999-2015)(Rosain et al., J.Infect Dis
2017)
- 16 patients in England with inherited or acquired complement
deficiencies (2008-2017) (Ladhani et al., BMC Infect Dis 2019).
8. Complement deficiencies and IMD: Isolates
Type of
deficiency
N° of isolates/episodes
(patients)
Isolates (n) Fatal
cases
TPD 63 (59) B(19); C(2); Y(29); W(9); E(4); NG(1) 1
Factor D 1 (1) B (1) 0
Properdin 1 (1) Y (1) 1
Eculizumab 3 (3) Y(2); C(1) 0
Rosain et al., J.Infect Dis 2017, El Sissy et al., Frontiers in Immunology 2019) : France 1999-2018
Type of deficiency N° of isolates/episodes
(patients)
isolates
Inherited 11(8) B(3); Y(7); NG(1)
Eculizumab 9 (8) B(3+3NG); Y(1); W(1);
E(1)
Ladhani et al., BMC Infect Dis 2019 : England 2008-2017
• Heterogeneous isolates
• Frequent Y, E and NG isolates
• Only 21% belonging hyper-invasive CC (France)
9. Coverage of serogroup B and E isolates of the
TPD patients by the 4CMenB vaccine
1
2
4
8
16
32
64
128
256
512
Before
After
hSBAtitreslog2
Serogroup ESerogroup B
Data NRC, Institut pasteur
10. Immunogenicity of MCC in a patient with
aHUS on eculizumab therapy
Zlamy et al., Pediatr Transplantation 2012:
A four-yr-old boy presented with aHUS
• TCC concentration reflects the ability to activate the complement system
• But SBA response seems to be impaired under treatment
Terminalcomplementconcentration(C5b-9)
inhealthydonors260and890lg/lL
Reduction of
eculizumab doses
TCC
SBA
11. Courtesy from Prof R. Borrow
Parikh SR et al. Pediatrics. 2017 Sep;140(3). pii: e20162452.
Case of IMD due to a vaccine-preventable and penicillin-resistant strain in a fully immunised
young adult (22 years) on long-term complement inhibitor therapy and daily penicillin
chemoprophylaxis.
First case of meningococcal group B vaccine failure in a young adult receiving Eculizumab
for aHUS.
Developed IMD due to capsular group B 4 months after receiving 2 doses of 4CMenB
vaccine while on oral penicillin prophylaxis.
Strain ST-162 (pathogenic potential).
Capsular gene SiaDb interrupted by an insertion sequence.
PenA allele contained 3 mutations associated with reduced penicillin sensitivity.
PenA allele previously associated with N. gonorrhoeae.
Strain confirmed covered by 4CMenB by MATS by NHBA antigen.
Penicillin-resistant case of IMD in patient on
Eculizumab therapy
15. Conclusions (1)
• Increasing evidence of association of complement activation and
degenerative diseases
• Anti-complement treatment may be benefic
• Complement deficiencies can be associated with increase susceptibility to
IMD.
• Serogroup Y isolates predominate but NG can be important under anti-
complement treatment
• Explore complement systematically when IMD is provoked with non
hyperinvasive isolates.
• Explore complement systematically if IMD with vaccine preventable
serogroup in vaccinated patients.
• If an inherited complement deficiency confirmed in the patient then explore
the members of the family.
• Exploration of not only the determination of the CH50 activity but also the
alternative pathway.
16. • Vaccination of subjects with complement deficiencies
(inherited and acquired) against ACWY and B
• Vaccination in not enough. Antibiotic treatment is
required (High dose penicillin V ≥ 250 000 IU/Kg/day).
• Rescue antibiotics (i.e. self-treatment with a treatment
course of amoxicillin (+ penicillin), ciprofloxacin or
other antibiotics to be defined when unwell)?
• Vaccination of household contacts of subjects with
complement deficiencies (cocooning strategy).
Conclusions (2)