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Effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and

Effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and functionally asplenic patients C. Forstner, S. Plefka, S. Tobudic, H.M. Winkler, K. Burgmann, H. Burgmann Department of Internal Medicine I Division of Infectious Diseases and Tropical Medicine

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Effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and

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  1. Effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and functionally asplenic patients C. Forstner, S. Plefka, S. Tobudic, H.M. Winkler, K. Burgmann, H. Burgmann Department of Internal Medicine I Division of Infectious Diseases and Tropical Medicine Medical University of Vienna Dr. Stephanie Plefka October 2014

  2. http://www.news.at/_storage/asset/1650080/storage/newsat:key-visual/file/12967091/spitaeler-akh-proben-311334_e.jpghttp://www.news.at/_storage/asset/1650080/storage/newsat:key-visual/file/12967091/spitaeler-akh-proben-311334_e.jpg

  3. Background Splenectomized and functionally asplenic patients are at an increased risk of overwhelming post-splenectomy infection (OPSI) and invasive pneumococcal disease (IPD) caused particularly by Streptococcus pneumoniae1: • Sepsis • Meningitis • Pneumonia 1 - Di Carlo I, Primo S, Pulvirenti E, Toro A. Should all splenectomised patients be vaccinated to avoid OPSI? Revisiting an old concept: an Italian retrospective monocentric study. Hepatogastroenterology. 2008 Mar-Apr;55(82-83):308-10. • - Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures ar not being followed. J Clin Pathol 2001; 54:214-8 • - Ejstrud P, Kristensen ´B, Hansen JB, Madsen KM, Schonheyder HC, Sorensen HT. Risk and patterns of bacteremia after splenectomy: a population-based study. Scand J Infect Dis 2000; 32:521-5 • - Kyaw MH, Holmes EM, Toolis F, Wayne B, Chalmers J, Jones IG, et al. Evaluation of severe infection and survival after splenectomy. Am J Med 2006; 110:276e1-7e.

  4. Background • Current guidelines2: Vaccination with the 23-valent pneumococcal polysaccaride vaccine (PPV23) after SPE Revaccination after 3-5 years • 2Davies JM, Lewis MPN, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs HB, Rewiewof guidelines for the prevention andtreatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British committee for standards in haematology by a working part if the haemato-oncology task force. Br J Haematol 2011; 155:308-17.

  5. Aims • Investigation of the effectiveness of pneumococcal vaccination, using PPV23 and PCV7, in preventing OPSI and IPD among patients after splenectomy and patients with a congenitally absent or dysfunctional spleen. • Induction of serological response

  6. Methods • Study Design Single-centre observational trial • Retrospective analysis • Prospective determination Ad a.) OPSI or IPD in post-splenectomized patients? Cause of death in deceased patients? Ad b.) Specific anti-pneumococcal antibody concentrations

  7. Methods • Material • Questionnaire (a.) • Database (a.) • Blood sampling (b.)

  8. Methods Retrospective analysis • Questionnaire • Demographic data • Reason and time of SPE/asplenia • Time and type of pneumococcal vaccination • Number and type of OPSI or IPD • Database Number and causes of death obtained from the local central bureau of statistics in Vienna

  9. Methods Prospective determination • Measurement of serological antibody response Comparison of antibody concentration • Vaccinated, splenectomized/asplenic patients • Age-matched control group of non-vaccinated, non-splenectomized patients • 7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) contained in PPV23 and PCV7 - ELISA • Excluded: revaccination

  10. Methods • Patients Criteria of Inclusion: • Splenectomy or functionally asplenic • Vaccination against Streptococcus pneumoniaebtw. 1996 and 2009 at AKH • Vaccines: - PPV23 (before March 2002) - PCV7 (replaced PPV23) • 19a – 90a

  11. Methods • Patients

  12. Methods • Limitations • Retrospective analysis of the post-vaccine complications • Serological responses • Determined only once • Limited number of patients • Irrespective of the time of vaccination

  13. Results

  14. Results • Cause of death • Progression of the underlying malignant haemato-oncological disease in 68% • Septic shock in 13.2% • 3 septicaemia as complication of pneumonia • 4 fulminant neutropenic sepsis • Underlying disease: 3 lymphoma 2 leukaemia 1 immunodeficiency 1 visceral leishmaniasis

  15. Results • Cause of death

  16. Results • Post-vaccine complications • OPSI • 7% of all study patients • Mortality 64% (7/11) • Diagnosed a median of 1.3a after vaccination • 1a in deceased • 2.9a in living • Cause of death: bacterial sepsis • Causative pathogen in survivers: Strep. Pneumoniae • No meningitis

  17. Results • Post-vaccine complications • IPD • 13% of living patients • Pneumonia in 9 • Septicaemia in 4 • Otitis media in 2 • No meningitis • Causative pathogen: Strep. Pneumoniae

  18. Results • Serological antibody response • PCV7 within the previous 5 years (n=15) • => significantly higher GMCs (of 0.8-6.1µg/mL) against all 7 Strep. Pneumoniae serotypes measured • 4, 6B, 9V, 14, 18C, 23F

  19. Results

  20. Results • Antibodies to Pneumococcal Polysaccarides 1) PPV23 2) PCV7 3) Control group * p < 0.05 # p < 0.001 GMC: mcg/ml Serotype

  21. Results • 7% OPSI between 1996-2009 (PPV23 and/or PCV7) • OPSI of a median of 1.3a after vaccination • 64% mortality • Causative pathogen: Streptococcus pneumoniae

  22. Results • PCV7 betw. 2005-2009 – all 46 splenectomized patients still alive in 2009 • PPV23 followed by PCV7 • All patients died • No OPSI

  23. Discussion • Main indication for splenectomy in all study patients: Malignant haematological neoplasm mostly Thrombocytopenia • Langley et al. 2010 • Melles et al. 2004 • Böhner et al. 1996

  24. Discussion • Main cause of death: Malignant haemato-oncological disease (68%) But: septic shock in 13.2%

  25. Discussion • Post-vaccine complications: 7% OPSI in all splenectomized and vaccinated patients All Sepsis, no meningitis • Ejstrud et al. 2000

  26. Discussion • Serological antibody response: Vaccination with PCV7 in the previous 5 years => High GMCs of 0.8-6.1mcg/mL against 4, 6B, 9V, 14, 18C, 19F, 23F • Meerwald-Eggink et al. • >0.35 mcg/mL against 4 and 9V • SPE, non-vaccinated 9/16 <0.35mcg/mLg

  27. Discussion • Serological antibody response: Vaccination with PCV7 in the previous 5 years -> No deceased => Thesis: High GMCs of 0.8-6.1mcg/mL might be a level to achieve protection

  28. Conclusion • Underlying diseases in splenectomized patients seem to be the most important predictors of mortality • High GMCs after pneumococcal vaccination within the first 5 years after vaccination • Post-vaccine pneumococcal sepsis in 3.3% of the splenectomized survivors

  29. Special thanks Univ. Prof. Dr. Burgmann Dr. Selma Tobudic Heide-Maria Winkler Secretary of Department

  30. Thank you for your attention • http://www.alpha-world.info/system/attachments/cms/430d1336395260-wien-special.jpg

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