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Vaccination anti pneumococcique: quel vaccin choisir? Dr. J.Janssens Service de néphro-immuno-infectiologie CHR citadelle Epidémiologie pneumocoque • Parmi les pneumococcies, les pneumonies sont de loin les plus fréquentes. Dans 20 à 50% des cas, elles sont associées à une bactériémie et sont donc invasives. • La mortalité associée aux pneumonies est de 5-10% si l’infection est non-invasive et de 5-35% si elle est invasive. Ces chiffres augmentent respectivement à 10-20% et 18-50% pour les personnes de plus de 65 ans. • Par ailleurs les infections invasives sont dans 90% des cas associées aux pneumonies, dans 5%, il s’agit de méningites . • En Belgique, l’incidence des infections invasives est de 15-45/100 000 pers. C’est un des taux les plus élevés en Europe. La comparaison de données entre différents pays doit cependant être réalisée avec précautions, car les systèmes de surveillance des infections invasives ne sont pas les mêmes . Major clinical forms of pneumococcal disease • • Pneumococcal disease can be broadly grouped into categories of invasive disease and noninvasive (also termed mucosal) disease1 Non-invasive forms of disease may become invasive (e.g., pneumonia when accompanied by bacteraemia)2 1. WHO. Acute Respiratory Infections (Update September 2009) http://www.who.int/vaccine_research/diseases/ari/en/index3.html Accessed October 24, 2011; 2. CDC. Epidemiology and prevention of vaccine-preventable diseases. 11th ed. 2009;217–230. More than 80 % of invasive pneumococcal disease (IPD) in older adults is bacteraemic pneumonia Distribution of clinical syndromes in IPD by age (Netherlands, 2004-2006) Jansen AG et al. Vaccine. 2009;27(17):2394-401. Invasive pneumococcal disease is a major cause of vaccine preventable deaths at the extremes of age USA, 2009 Incidence of IPD and associated mortality rates 1. 2. Centers for Disease Control and Prevention. 2010. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2009. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine Preventable Diseases. The Pink Book. 11th Edition. May 2009 • Incidence of IPD increases from 50 years of age onwards • IPD carries a high mortality rate, with an average of 20% in adults with bacteraemic pneumonia1,2 S. pneumoniae serotypes isolated from patients hospitalised with IPD in 10 countries (1998 to 2001) Number of isolates Hospitalised patients ≥15 years of age with IPD (N=796)* Serotypes IPD=Invasive Pneumococcal Disease. *South Africa, US, Sweden, Spain, New Zealand, Taiwan, Argentina, Brazil, Hong Kong, France. Alanee SR, et al. Clin Infect Dis. 2007;45:46-51. Invasive pneumococcal disease is commonly caused by antibiotic-resistant strains1-3 Proportion Antibiotic strains 1. 2. 3. Antibiotic-resistant strains may3 •complicate treatment decisions •cause treatment failures and •increase treatment duration and cost of care European Antimicrobial Resistance Surveillance Network (EARS-Net). Antimicrobial resistance surveillance in Europe 2009; http://ecdc.europa.eu/en/publications/Publications/1011_SUR_annual_EARS_Net_2009.pdf Accessed 25 May 2011 Liñares J et al. Clin Microbiol Infect. 2010;16:402-410; Kyaw MH et al. N Engl J Med. 2006;354:1455-1463. Pneumocoque: Pathogénie et Portage PORTAGE - INFECTION Nasopharyngeal carriage may occur in up to 60% of healthy pre-school children and up to 30% of healthy older children and adults Nasal cavity Asymptomatic carrier Nasopharynx: site of colonisation Aerosol Trachea Inhalation Patient with pneumococcal disease Dissemination Print master On constate donc un parallèle entre colonisation et infection sauf Chez la personne âgée où le mécanisme doit être différent. Facteurs influençant la colonisation Le taux de lymphocytes T CD4 Le taux de lymphocytes T CD4 des muqueuses ORL Lymphocytes muqueux ORL • Production d’interleukine 17 et un peu d’interleukine 22 par les lymphocytes T CD4 ( auxilliaires). • L’interleukine 17 agit sur les tissus via un récepteur qui permet notamment aux IGA muqueux de passer depuis la sous muqueuse vers la muqueuse. • Elle agit également comme pro inflammatoire et activateur des neutrophiles. • Elle prévient donc ainsi la colonisation par le pneumocoque. • A signaler aussi que en Belgique une 1/400 est déficiente en IGA. Facteurs prédisposants Facteurs prédisposant à une déficience en lymphocytes T CD 4 Muqueux producteurs d’interleukine 17 Age Immunodéficience T( infection par le virus HIV) Immunosuppresseurs ( y compris les corticoïdes inhalés). Allergie. Stress aigu ( infarctus du myocarde, AVC,…). Role du tabac Fumer neutralise les peptides antimicrobiens , un fumeur a donc 4 fois plus d’être colonisé par le pneumocoque Role de l’alcool Mécanisme d’action des CD4 Les polymorphonucléaires sont incapables de phagocyter le pneumocoque Sans immunoglobulines Les vaccins anti pneumococciques La plupart des lymphocytes B ont besoin de l’aide des Lymphocytes T pour: 1. orienter la production d’anticorps vers les IGG et plus particulièrement vers les IGG3 plutôt que vers les IGM. 2. Multiplier le nombre de lymphocytes B producteurs d’anticorps 3. Se différencier en cellules mémoires. Generating a different immunological response Plain Polysaccharide Vaccine Conjugated Vaccine Polysaccharide antigens Polysaccharide antigens Immunogenic carrier protein Conjugated vaccine 1.Pollard AJ et al. Nature Reviews Immunology. 2009;9(3):213-20. By covalently linking polysaccharide antigens to a carrier protein, polysaccharide specific memory B cells are produced, leading to the potential for a memory response1 Polysaccharide vaccines: T-independent immune response Primed Polysaccharide antigens 1. 2. 3. 4. Plain polysaccharide vaccines:1-4 Lazarus R et al. Clin Infect Dis 2011;52(6):736-42; Pollard AJ et al. Nature Revi Immuno. 2009;9(3):213-20; Ada G. N Engl J Med. 2001;345:1042-1053 Douglas, R et al Am J Dis Child. 1986;140(11):1183-1185. •Activate B cells, but do not generate helper T cells •Do not induce long-lasting immunological memory •No impact on nasopharyngeal carriage Conjugated vaccines: Generating a T- dependent immune response Naïve Conjugated vaccine Conjugated vaccines:1-5 •Require ~10 times less antigens (Pneumococcal Conjugate Vaccines)* •Induce immunological memory •Induce booster response (Demonstrated in children) •Produce higher affinity IgG antibodies •Reduce nasopharyngeal carriage** * Example, for every 25g of polysaccharide antigen per serotype required for PPV, 2.2 g of polysaccharide antigen per serotype is required for PCV (except 6B for which 4.4 g of polysaccharide antigen is required), ** Demonstrated in children 1. Pneumovax SmPC; 2. Prevenar Summary of Product Characteristics; 3. Lazarus R et al. Clin Infect Dis 2011;52(6):736-42; 4. Pollard AJ et al. Nature Reviews Immunology. 2009;9(3):213-20; 5. Ada G. N Engl J Med. 2001;345:1042-1053. Marked reduction in the incidence of IPD since the introduction of PCV7 Denmark1 England & Wales2 Age specific incidence rates of laboratory confirmed IPD cases in the pre-Prevenar (2000–2007) and post-Prevenar (2008) periods Adjusted incidence of IPD per 100,000 population in children under the age of 2 years, 2000-2006 vs 2009-2010, England and Wales 1. Harboe ZB et al. Vaccine. 2010 Mar 19;28(14):2642-7; 2. Miller E et al, Lancet Infect. Dis. 2011; 11:760-768 All cause pneumonia hospitalisation for children <2 years declined by 39% over 4 years after the introduction of PCV7 Trends in monthly all cause pneumonia hospitalisation rates before and after routine immunisation of children with PCV7 Grijalva CG et al. Lancet. 2007;369:1179-1186. PCV7 in vaccine naïve adults ≥70 years of age • Design – Randomised, open-label, phase II study including 27 German centres – 219 ambulatory, vaccine naïve adults ≥70 years of age – Subjects immunised at study entry (dose 1) received a second immunisation after 1 year (dose 2). PCV7 immune response and the ability to suitably prime for booster responses to a second administration were assessed de Roux, A et al. (2008) Clinical Infectious Diseases, 46(7): 1015-1023 PCV7 elicits improved immune responses and immunological memory in elderly adults • In the study of De Roux et al, it was demonstrated that: – With a conjugate, immune response may be more robust – Beginning with a conjugate, revaccination with a conjugate may be possible – Beginning with a plain polysaccharide can blunt the immune response to subsequent conjugate – With a conjugate, immunologic memory may be induced de Roux A et al. Clinical Infectious Diseases. 2008;46(7):1015-1023. The functional antibody response to PCV7 observed in PPV naïve adults Functional antibody response* to PCV7 in PPV-naïve adults ≥ 70 years of age after a single dose (N=110)1 Adults ≥ 70 years of age Immunogenicity of Prevenar after 1 dose * OPA GMT Comparision of PCV vs PPV in elderly adults. Randomised, open-label, phase II study including 27 German centres. 219 ambulatory, vaccine naïve adults ≥70 years of age 1. De Roux, A., B. Schmöele-Thoma, et al. (2008) Clinical Infectious Diseases 46(7): 1015-1023 Take home message 1 Ne pas songer au vaccin pneumococcique uniquement quand on Pense splénectomie ou personne de plus de 65 ans 2 Songer à vacciner les catégories à risques: les tabagiques, les BPCO, les décompensés cardiaques, les diabétiques, les Immunodéprimés primaires ou secondaires, les insuffisants hépatiques et rénaux, les personnes agées 3. La vaccination par un vaccin polysaccharidique ne contre indique pas l’administration ultérieure chez le patient 4. Le vaccin peut et doit être administré chez les immunodéprimés Bon Après midi