effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and functionally...
TRANSCRIPT
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 IDivision of Infectious Diseases and Tropical Medicine
Medical University of Vienna
Dr. Stephanie PlefkaOctober 2014
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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.
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; 155:308-17.
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
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 determinationMeasurement 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. 1996 and 2009 at AKH Vaccines: - PPV23 (before March 2002)
- PCV7 (replaced PPV23) 19a – 90a
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 pneumonia4 fulminant neutropenic sepsisUnderlying disease: 3 lymphoma
2 leukaemia
1 immunodeficiency
1 visceral leishmaniasis
Results
Post-vaccine complications
OPSI 7% of all study patientsMortality 64% (7/11)Diagnosed a median of 1.3a after vaccination
1a in deceased 2.9a in living
Cause of death: bacterial sepsisCausative pathogen in survivers: Strep.
PneumoniaeNo meningitis
Results
Post-vaccine complications
IPD13% of living patients
Pneumonia in 9Septicaemia in 4Otitis media in 2
No meningitisCausative pathogen: Strep. Pneumoniae
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
Results
Antibodies to Pneumococcal Polysaccarides
Serotype
1) PPV23
2) PCV7
3) Control group * p < 0.05# p < 0.001
GMC: mcg/ml
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
Results
PCV7 betw. 2005-2009 – 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. 2010
Melles et al. 2004
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 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
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
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