1 / 86

Uso dei vaccini nell’adulto

Giampiero Carosi. Istituto di Malattie Infettive e Tropicali Università degli Studi di Brescia. Uso dei vaccini nell’adulto. VII° Congresso Nazionale SIMIT Bergamo, 19 –22 Novembre 2008. Vaccine role in the health of nations.

etenia
Download Presentation

Uso dei vaccini nell’adulto

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Giampiero Carosi Istituto di Malattie Infettive e Tropicali Università degli Studi di Brescia Uso dei vaccini nell’adulto VII° Congresso Nazionale SIMIT Bergamo, 19 –22 Novembre 2008

  2. Vaccine role in the health of nations • Immunisation and provision of clean water are, among all public health interventions, those with the greatest impact on world’s health • Vaccines are among the most cost-effective health interventions available World Health Organisation World Bank

  3. Goal of vaccine interventions in infants and children Vaccines are often such a powerful tool that they can make elimination of a specific disease an achievable target. The required components of an effective recepy are: • High effectiveness • Extensive coverage • Herd immunity effect

  4. Herd immunity • Successful vaccination protects immunised individuals from infection, thereby decreasing the percentage of susceptible persons within a population and reducing the possibility of infection transmission to others. • At a definable prevalence of immunity, an infectious organism can no longer circulate freely among the remaining susceptibles

  5. Smallpox: the only example of a successful eradication campaign(May 8th, 1980)

  6. Other intermediate effects On the way of elimination, vaccines may deeply change the clinical history of a medical condition by decreasing the incidence of a specific agent or shifting the epidemiologic pattern of an infection from epidemic to endemic

  7. Notified bacterial meningitis cases, Italy 1994 - 2008 Source: Sistema di Sorveglianza meningiti batteriche SIMI-ISS

  8. Hib conjugate vaccine This vaccine both elicits durable immunity by the time maternal-derived antibodies dissipate, and reduces nasopharyngeal carriage thus diminishing the risk of transmission

  9. Just by chance ? Effective vaccines are not available for: • AIDS • tuberculosis • malaria the biggest health problems that we are facing today

  10. Factors causing decreased acceptability of vaccines • Awareness of disease threats is decreasing (as a consequence of vaccine efficacy !!!!): measles, polio, etc. • Some segments of the public are unwilling to accept any risk of vaccine associated vaccination…. missing the need to make cost-benefit balances Vaccines are under attack as a cause of neurodevelopmental disorders, autoimune disorders, etc.

  11. CDC’s review of VAERS reports concerning Gardasil: • As at June 30 2008, 9749 reports of adverse events after Gardasil administration over an estimate of at least 8 million women receiving the vaccine. • 93% non serious: syncope, pain at the injection site, headcahe, nausea, and fever. Risk of fainting added to Gardasil prescribing information • 7% serious: death, Guillain-Barré syndrome (GBS) and thromboembolic disorders.

  12. CDC’s review of VAERS:Gardasil and GBS • According to CDC and FDA analysis no evidence that Gardasil vaccinated women have an increase of the baseline 1 to 2 per 100,000 incidence of GBS in the general population • No changes to any of the existing HPV recommendations • Close to publication the data of the Vaccine Safety Datalink (VSD) project comparing a vaccinated (> 300,000 doses) and an unvaccinated population on the risk of 9 specific important outcomes including GBS

  13. Polio vaccination in Italy • Polio 1,2,3 live attenuated vaccine (OPV, Sabin) more immunogenic than inactivated vaccine (IPV, Salk) but rarely associated with polio-like disease • After polio eradication in Italy, based on a risk / benefit analysis, IPV replaced OPV for infant and adult vaccination

  14. Adult immunization strategies • Rather than elimination, the aim is the reduction of morbidity/mortality in specific population groups • Increased risk of morbidity • Influenza, invasive pneumococcal disease for the elderly • Cervical cancer in women • Increased exposure • Vaccine preventable diseases in travellers • Influenza among health staff, etc.

  15. Summary (1) • Vaccines have a great potential among public heath prevention strategies • Demonstrated remarkable achievements at very attractive costs • The development of vaccines for the major endemic infectious diseases are a priority for current and future research

  16. Professor zur Hausen, Nobel Prize winner in Medicine 2008 for his research on HPV

  17. Life time risk 3-4% ESTIMATES OF THE WORLDWIDE INCIDENCE OF CERVICAL CANCER BREAST 1.050.346 CERVIX UTERI 470.606 445.963 COLON/RECTUM < 91.5 < 25.3 < 33.2 GLOBOCAN 2002 LUNG 337.115 < 9.7 < 15.4 STOMACH 317.883

  18. La struttura del virus La superficie esterna del virus è costituita da due proteine capsulari: L1 and L2 Il capsomero è costituito da 72 pentameri, ciascuno formato da 5 molecole di L1 1 molecola di L2 è incastonata nella cavità centrale del pentamero Gli anticorpi neutralizzanti riconoscono epitopi conformazionali di L1 Non sono noti in natura anticorpi neutralizzanti diretti verso L2

  19. La protezione è associata alla produzione di anticorpi neutralizzanti1 Anticorpi non neutralizzanti non prevengono l’infezione da HPV Anticorpi neutralizzanti prevengono l’infezione da HPV Infezione – assenza di anticorpi Recettore cellulare 1. Chen XS, Garcea RL, Goldberg I, et al. Molecular Cell. 2000;5:557–567.

  20. Vaccini basati su VLPs • Aventis Pasteur MSD / Merck vaccino quadrivalente per tipi • 6, 11 (condilomatosi) e 16, 18 (carcinoma della cervice) • Manifattura delle VLPs in S. cerevisiae • Adiuvante • Alluminio idrossifosfato solfato amorfo (AAHS)

  21. Vaccini basati su VLPs • GSK vaccino bivalenteper tipi • 16, 18 (carcinoma della cervice) • Manifattura delle VLPs su colture cellulari di insetti infettate da baculovirus • Adiuvante • Idrossido d’alluminio + • 3-O-deacilato-monofosforil lipide A (AS04)

  22. L’adiuvante AS04. Cellule B di memoria HPV16 HPV18 16000 3000 3.6 x* Q3 2.2 x Q3 12000 2000 = AS04 Frequenza di cellule B anti-HPV specifiche 8000 = [Al(OH)3] Median 1000 4000 Median Q1 Q1 0 0 pre day 60 day 210 pre day 60 day 210 vaccinazione vaccinazione Vaccino GSK anti HPV formulato con AS04 induce cellule B di memoria anti-HPV 16/18 specifiche Giannini SL, et al. Vaccine 2006; 24: 5937–49 * statistically significant (p <0.05, Wilcoxon’s test)

  23. Determinants for the cost-effectiveness analysis of HPV vaccines • Protective efficacy: virtually 100% on TARGET TYPES and provided that HAD NOT OCCURRED prior to vaccination • Health benefits: delayed impact on cervical cancer, early impact on cervical dysplasia and genital warts • Cost of the vaccine • Duration of protection

  24. Risposta B memory e durata della protezione vaccinica • Dose booster a 60 mesi dopo ciclo iniziale: • 1 settimana dopo il re-challenge titoli anticorpali simili 1 mese post primo ciclo • Sierotitoli più elevati 1 mese dopo il rechallenge rispetto ad 1 mese post primo ciclo Olsson SE, Vaccine 2007, 25: 4931 - 4939 Efficacia vaccinica duratura, forse life-long

  25. Pneumococcal Disease: Pathogenesis Colonization Crossing of mucosal barrier Local invasion Invasion of bloodstream Otitis media, sinusitis, nonbacteremic pneumonia Bacteremic pneumonia Meningitis Sepsis

  26. Indicazioni attuali vaccino antipneumococcico in Italia 23 valente 7 valente SOGGETTI >65 anni SOGGETTI <2 anni SOGGETTI 2-64 anni SOGGETTI 2-5 anni Condizioni ambientali Disordini immunitari Asplenia/Splenectomia Emopatie (anemia a cellule falciformi/talassemia) Immunodeficit congeniti/acquisiti Disordini immunitari Asplenia/Splenectomia Emopatie (anemia a cellule falciformi/talassemia) Immunodeficit congeniti/acquisiti Patologie “croniche” CARDIOPATIE Diabete mellito Epatopatie/Nefropatie Patologie croniche BPCO/CARDIOPATIE Diabete mellito Epatopatie/Nefropatie Malformazioni Traumi cranici con fistole Malformazioni Traumi cranici con fistole

  27. Conjugated and un-conjugated pneumococcal vaccines • Conjugated vaccines (but not polisaccharide vaccines) induce mucosal immunity. • These vaccines are effective in reducing bacterial colonisation and carrier state • They exert a significant herd immunity effect which is not demonstrated for polisaccharide vaccines Nurkka A et al., 2001

  28. Reduction of invasive pneumococcal disease in <5 children 97% reduction CDC unpublished data and MMWR Sep 16, 2005

  29. PCV7 introduction % Change 2003/4 vs 98/99 >80: -77% (-82,-71) 65-79: -74% (-79,-67) 50-64: -64% (-70,-57) 18-49: -76% (-80,-72) >80 y 65-79 y 50-64 y 18-49 y Reduction of invasive pneumococcal disease in unvaccinated adults Moore et. al. 2006 ICEID

  30. 160 Vaccine introduced 140 120 100 80 Penicillina sensibili Incidence (cases per 100,000) 60 Penicillina-resistenti 40 20 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 Riduzione delle patologie invasive da pneumococco resistenti alla pennicillina in bambini sotto i 2 anni Kyaw, M. H. et al. N Engl J Med 2006;354:1455-1463

  31. Vaccino antipneumococcico e obiettivi di salute in Italia • Obiettivo: ridurre morbidità da malattia pneumococcica nei < 5 anni • Stimando incidenza 60 / 100k, efficacia 90%, copertura 90%, share tipi vaccinali 80%  prevenzione 900 casi / anno • Efficacia certa, ma costo-efficacia diversamentevalutata dalle regioni (alti costi attuali del vaccino - attuale difficoltà in misurare morbidità)

  32. Summary (2) • Adult vaccination strategies aim at morbidity reduction rather than disease elimination • Vaccine targets are derived by a thourough comprehension of disease impact in specific population groups • The benefits of several effective adult vaccines (including HPV, pneumococcus, etc.) might be better exploited

  33. Il vaccino per l’influenza stagionale Il Ministero della Salute sulla base dell’evidenza che la vaccinazione antiinfluenzale riduce la malattia in soggetti sani adulti del 70 – 90% e la mortalità per influenza nell’anziano del 40 – 75%, raccomanda la vaccinazione a: • persone con età maggiore di 64 anni • bambini di età > 6 mesi con comorbidità • bambini in trattamento cronico con ASA • adulti affetti da patologie croniche • donne che saranno in 2-3 trimestre di gravidanza all’epoca del picco epidemico • ospiti di lungodegenze • personale sanitario • persone a contatto con soggetti ad alto rischio di complicanze • soggetti addetti a mansioni pubbliche di primario interesse • soggetti a contatto con animali potenzialmente affetti da ceppi aviari Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07”

  34. Target di copertura vaccinale in Italia Target minimo 70%, ottimale 100% Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07” Copertura vaccinale effettiva in Italia 60% in anziani, adulti con co-morbidità 1.4% personale sanitario 8.2%, addetti a servizi di primario interesse 2.5% Piano Nazionale Vaccini 2003-2005 Ministero della Salute: “Prevenzione e controllo dell’influenza: raccomandazioni per la stagione 2006-07”

  35. Preparedness for the influenza pandemic . • Drugs • antivirals • othres (antibiotics) • Vaccines • pandemic • Pre-pandemic • Social distancing Global plan

  36. Influenza vaccines • Vaccines are the mainstay for prevention of seasonal flu since half a century • A pandemic vaccine will be developed, but impact on the pandemic low because of delayed availability • Pre-pandemic vaccines developed to gain time. New adjuvants and new production techniques been developed (antigen sparing). Assumptions • Low efficacy ~30% (mismatch, one dose) • New adjuvants allow broaden efficacy on drifted strains • Priming may be done with one or two doses

  37. Development of the vaccine strategy DECLARATION OF PANDEMIC 2^ DOSE PROTECTION 1^ DOSE 1^ DOSE 2^ DOSE PROTECTION PROTECTION 1^ DOSE 2^ DOSE 3^ DOSE PANDEMIC VACCINE PRE-PANDEMIC VACCINE

  38. Case fatality rate > 60% in human cases of avian influenza 2% in 1918 pandemic 0.2% in 1957 pandemic < 0.1% in seasonal flu

  39. Ruolo del vaccino nel piano pandemico italiano Nella fase 3, caratterizzata da presenza di un nuovo sottotipo virale, ma assenza di trasmissione interumana, è necessario identificare le categorie prioritarie a cui offrire la vaccinazione pandemica. Il presente Piano identifica 6 categorie, elencate in ordine di priorità: 1. Personale sanitario e di assistenza (ospedali, …) 2. Personale addetto ai servizi essenziali alla sicurezza e alla emergenza (polizia, …) 3. Personale addetto ai servizi di pubblica utilità (esercito….) 4. Persone ad elevato rischio di complicanze severe o fatali a causa dell’influenza 5. Bambini e adolescenti sani di età compresa tra 2 e 18 anni 6. Adulti sani Ministero della Salute. Piano nazionale di preparazione e risposta ad una pandemia influenzale. 2006

  40. Pandemic severity index CDC 2007: available at www.pandemicflu.gov

  41. Summary (4) • We keep on waiting the next influenza pandemic • Models predict that its severity might be substantial, and, mostly, unpredictable beforehand • A comprehensive vaccination strategy, which include the use of seasonal influenza, pre-pandemic and pandemic vaccines, will be a mainstay of health system response.

  42. Immunization of the International Traveler 1) Routine immunizations (measles, polio, dT, influenza, etc.) 2) Routine travel immunizations (Hep. A, typhoid, etc.) 3) Host country required immunizations (yellow fever) 4) Geographic risk immunizations (JE, meningococcus, TBE, etc.) 5) Extended stay immunizations (Hep B, rabies, etc) 6) Which vaccination for which traveller? 7) When are you leaving? Tomorrow … 8) Vaccine/drugs interactions

  43. Immunization of the International Traveler No (update) 3) Host country requirements? 2) Routine Travel immunization updated? yes 1) Ruotine immunization updated? yes yes No (update) No (update) READY TO GO! 5) Extended stay immunization updated? 4) Geographic risk updated? yes yes No (update) Thanassi e Weiss, 1997; 43-70 No (update)

  44. Booster of tetanus vaccine in adults 1 dose IM (0.5 mL – 40 IU) Diphteria-tetanus vaccines dT Diphteria 2 IU (instead of 30) To avoid local and rare systemic adverse events

  45. Incidence of Hep A 100 times that of Typhoid 1000 times that of cholera

  46. Hepatitis A: vaccine characteristics Very well tolerated Immunogenic: 58% at w2, 97% at w4 Vaccinate 4 wks before departure

  47. TwinrixTM Update • Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine • Accelerated dosing schedule of 0, 7, 21-30 days and a booster dose at 12 months • FDA approved March 28, 2007

More Related