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

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 pneumoniae 1 : 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 Mar-Apr;55(82-83): Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures ar not being followed. J Clin Pathol 2001; 54: 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: 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.

Background Current guidelines 2 : Vaccination with the 23-valent pneumococcal polysaccaride vaccine (PPV23) after SPE Revaccination after 3-5 years 2 Davies 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:

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

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

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

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

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

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

Methods Patients

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

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

Results Cause of death

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

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

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

Results

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

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

Results PCV7 betw – all 46 splenectomized patients still alive in 2009 PPV23 followed by PCV7 All patients died No OPSI

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

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

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

Discussion Serological antibody response: Vaccination with PCV7 in the previous 5 years => High GMCs of mcg/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

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

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

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

Thank you for your attention