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

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 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

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

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

Cause of death

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

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

Thank you for

your attention

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