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2 MJA 2009, 191:142 2

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5 CDC Interim Recommendations for Oseltamivir and Zanamivir Patient Categories for Treatment 1.Recommended: all patients hospitalized with suspected or confirmed influenza 2.Recommended: persons with warning symptoms (dyspnea, etc) or signs (tachypnea, oxygen desaturation) of lower respiratory tract illness 3.Generally recommended: persons at risk for complications with confirmed or suspected influenza, including: children under 5 years old; pregnant women; adults over 65 years of age; persons under 19 years of age on long-term aspirin therapy; and persons with chronic predisposing conditions or immunosuppression. The recommended treatment is either oseltamivir or zanamivir, with additional treatment considerations listed below. samedi 17 octobre

6 Other Treatment Considerations 1.Clinical judgment is always important. 2.The recommendations apply to persons with confirmed or suspected influenza. 3.Treatment should not be delayed to establish the diagnosis. 4.The rapid tests show sensitivity of only 10%-70%. The appropriate test to rule out H1N1 is the rrt-pcr. 5.Patients at high risk for complications might be given prescriptions for antivirals to fill after telephone consultation. 6.Some experts recommend double-dose antivirals in some severely ill patients (but there are no published data to support this). 7.More than 99% of seasonal influenza A (H1N1) strains were resistant to oseltamivir in the season, but few of those strains have been detected since April 21, Therefore, the recommendation is to use oseltamivir or zanamivir until national surveillance data show a need for an alternative strategy. (Surveillance data are updated weekly. For guidance on empiric treatment when multiple strains are circulating, see the CDC's Health Alert Network). samedi 17 octobre

7 Lancet Infect Dis 2009, 9:

8 Lancet Infect Dis 2009, 9:

9 Lancet Infect Dis 2009, 9:

10 Lancet Infect Dis 2009, 9:

11 Anti influenza drug for healthy adults Median time to symptom aliviation Zanamivir : 0,57 days Oseltamivir : 0,55 days Adult at risk Zanamivir : 0,98 days Oseltamivir : 0,74 days Complications : little information, very few events. Only single trial in children with asthma samedi 17 octobre

12 JAC 2003, 51:

13 JAC 2003, 51:

14 Cllin Infect Dis 2005, 40:

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16 Issues in Antiviral Prophylaxis Consider oseltamivir or zanamivir prophylaxis in the following circumstances: 1.In persons at high risk for complications plus exposure* 2.In healthcare workers, public health workers, or first responders plus exposure* 3.To control outbreaks in closed or semi-closed settings, such as nursing homes and correctional institutions * Exposure no longer than 48 hours after contact with a person with confirmed, probable, or suspected 2009 H1N1 or seasonal flu during the contagious period (defined as 1 day before symptoms until 7 days after onset of illness). Antiviral prophylaxis is not recommended for healthy children or adults exposed in community, school, camp, or similar settings. Note the 3 special circumstances listed above. samedi 17 octobre

17 Tamiflu, immunocompétent: prophylaxie samedi 17 octobre

18 Influenza post exposure prophylaxis Oseltamivir, household, RR0,19 ( ) Zanamivir, household, RR0,21 ( ) samedi 17 octobre

19 Safety and efficacy of extented duration antiviral chemoprophylaxis against pandemic and seasonal influenza Trials involving 7021 participants Decrease of frequency of symptomatic influenza RR0,26 ( ) But not asymptomatic influenza RR1,03 ( ) No effect of vaccination No study in children younger than 12 years Oseltamivir = Zanamivir samedi 17 octobre 2009 Ann Intern Med 2009, 151(7) 19

20 Meta-analysis of laboratory-confirmed symptomatic influenza Khazeni, N. et. al. Ann Intern Med 2009;0: E-143 samedi 17 octobre

21 Tamiflu et immunosuppression: traitement Plusieurs études prospective ou rétrospective, non randomisées, peu de patients Interprétation des résultats!!! Bonne tolérance samedi 17 octobre

22 Tamiflu et immunosupression: prophylaxie Abstract, étude randomisée prospective( 477 patients) portant sur l efficacité et la sécurité d un traitement préventif prolongé (12w) par Tamiflu pour la grippe chez l immunosupprimé.(greffé organe ou moelle) Diminution du cas de grippe symptomatique ou asymptomatique ( 8.4 versus 2.1%) Effets secondaires: GI (22%placebo, 21%) 2 décès dans le groupe placebo. Roche. samedi 17 octobre

23 JAMA 2009, 301:

24 JAMA 2009, 301:

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26 Vaccine efficacy Healthy children and adults % if good matched 0 50 % if bad matched Live attenuated vaccine : % better protection than inactivated vaccine samedi 17 octobre

27 Lancet Infect Dis 2009, 9:493 27

28 Lancet Infect Dis 2009, 9:493 28

29 Influenza in immunosuppressed populations Available data suggest that Most immunosuppressed patients are at higher risk of influenza-associated complications (mortality 0 33 %) Impaired humoral vaccine responses Quid cellular immunity? Safe vaccination Vaccine efficacy : only one study in HIV (HHART) infected patients : high efficacy samedi 17 octobre 2009 Lancet infect dis 2009, 9:493 29

30 Effectiveness and Cost-Effectiveness of Vaccination Against Pandemic Influenza (H1N1) Data sources : literature and expert opinion Results of Base-Case Analysis: Assuming each primary infection causes 1.5 secondary infections, vaccinating 40% of the population in October or November would be cost-saving. Vaccination in October would avert 2051 deaths, gain QALYs, and save $469 million compared with no vaccination; vaccination in November would avert 1468 deaths, gain QALYs, and save $302 million. Results of Sensitivity Analysis: Vaccination is even more cost-saving if longer incubation periods, lower rates of infectiousness, or increased implementation of nonpharmaceutical interventions delay time to the peak of the pandemic. Vaccination saves fewer lives and is less cost-effective if the epidemic peaks earlier than mid-october. Limitations: The model assumed homogenous mixing of case-patients and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. Additional costs and savings not included in the model would make vaccination more cost-saving. samedi 17 octobre 2009 Ann Intern Med 2009,

31 CDC H1N1 vaccine priority groups Pregnant women Household contact of infants younger than 6 months Healthcare and emergency services personnel Individuals between 6-24 years Individuals aged 25 years or older with underlying conditions If supplies are not sufficient, ACIP recommend exclusion of Individual aged 5-18 years (w/o risk factor) Healthcare worker without direct contact with patients Individual aged 25 years or older with underlying condition PS : 65 years or older : rare (1 % of confirmed cases) years : very few samedi 17 octobre 2009 JAMA

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33 JAMA

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35 JAMA

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37 NEJM 2009,

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44 PPV vs placebo : Invasive pneumococcal disease Vaccine Control Odds ratio All studies N= OR 0.26 (S) Adults in high income countries N= OR 0.20 (S) Adults in high income countries with chronic illness N= OR 1.56 No protection? Lack of power? IPD vaccine types only N= OR 0.18 Cochrane Database of Systematic Reviews, Issue 3, 2009 samedi 17 octobre

45 PPV vs placebo : Mortality all causes Vaccine Control Odds Ratio All studies N= OR 0.87 (NS) Adults in high income countries N= OR 0.84 (NS) Adults in high income countries with chronic illness N= OR 1.04 (NS) Cochrane Database of Systematic Reviews, Issue 3, 2009 samedi 17 octobre

46 PPV vs placebo : Mortality due to pneumoniae Vaccine Control Odds ratio N= (NS) Cochrane Database of Systematic Reviews, Issue 3, 2009 samedi 17 octobre

47 PPV vs placebo : pneumonia all causes Vaccine Control Odds ratio All studies N= (S) Adults in high income countries N= (NS) Adults in high income countries with chronic illness N= Not protective efficacy? Lack of power? Cochrane Database of Systematic Reviews, Issue 3, 2009 samedi 17 octobre

48 PPV vs placebo : Pneumococcal pneumonia Vaccine Control Odds ratio Definitive pneumococcal pneumonia N= (S) Definitive pneumococcal pneumonia (vaccine types only) N= (S) samedi 17 octobre

49 Vaccines for preventing pneumococcal infection in adults (review Cochrane) Conclusion méta-analysis Cochrane This meta-analysis supports the use of pneumococcal polysaccharide vaccine to prevent IPD in adults, particularly otherwise healthy adults, in developed and developing country settings. The evidence from our meta-analysis of RCTs does not support the routine use of pneumococcal polysaccharide vaccine to prevent all-cause pneumonia or mortality samedi 17 octobre

50 Effectiveness of Pneumococcal Polysaccharide Vaccine in Older Adults Lisa A. Jackson, M.D., M.P.H., Kathleen M. Neuzil, M.D., M.P.H., Onchee Yu, M.S., Patti Benson, M.P.H., William E. Barlow, Ph.D., Annette L. Adams, M.P.H., Christi A. Hanson, B.A., Lisa D. Mahoney, M.P.H., David K. Shay, M.D., M.P.H., William W. Thompson, Ph.D. and the Vaccine Safety Datalink Retrospective study of more than 47,000 persons patients > 65 ans period : 3 years Outcome : hospitalisation because of community-acquired pneumoniae Outpatient pneumoniae Pneumococcal bacteriemia N Engl J Med Volume 348;18: May 1, 2003 samedi 17 octobre

51 Effectiveness of Pneumococcal Polysaccharide Vaccine in Older Adults Vaccination was associated with a significant reduction in the risk of pneumococcal bacteremia, but over three years of follow-up there was no reduction in the risk of communityacquired pneumonia (hazard ratio, 1.07) Although pneumococcal vaccination helps protect older persons against life-threatening bacteremia, it provides little if any protection against pneumonia Other strategies are needed to prevent the nonbacteremic manifestations of pneumococcal infection samedi 17 octobre

52 Vaccine 2008, 26:

53 Vaccine 2009, 275:C9-C14 53

54 Vaccine 2009, 275:C9-C14 54

55 Vaccine 2009, 275:C9-C14 55

56 Vaccine 2009, 275:C9-C14 56

57 Influenza associated mortality in 1918 Less than 5 % of death occurs in 3 days after downset of symptoms Serotype distribution among patients with pneumococcal pneumonia before and after 1918 pandemic : very different samedi 17 octobre

58 Lancet Infect Dis 2009, 9:493 58

59 Lancet Infect Dis 2009, 9:493 59

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