Folie 1

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/newsatkey-visual/file/12967091/s
pitaeler-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-Apr55(82-83)308
  -10.
• - Waghorn DJ. Overwhelming infection in asplenic
  patients current best practice preventive
  measures ar not being followed. J Clin Pathol
  2001 54214-8
• - 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 32521-5
• - 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 110276e1-7e.

4
Background

• Current guidelines2
• 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
  155308-17.

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 pneumoniae btw.
  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 (n15)
• gt 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 lt 0.05
p lt 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
• gt High GMCs of 0.8-6.1mcg/mL against
• 4, 6B, 9V, 14, 18C, 19F, 23F
• Meerwald-Eggink et al.
• gt0.35 mcg/mL against 4 and 9V
• SPE, non-vaccinated 9/16 lt0.35mcg/mLg

27
Discussion

• Serological antibody response
• Vaccination with PCV7 in the previous 5 years
• -gt No deceased
• gt 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