What vaccines should be administered to adult, splenectomized, patients?

Introduction: the spleen

The spleen is an organ that is about the size of a fist and can become enlarged by infection.1 About 6% of the body’s cardiac output goes to the spleen, which comprises a quarter of the body’s lymphoid mass and half of the body’s monocytes and B lymphocytes. Therefore, the spleen is an important organ that helps fight infection, through its involvement with filtration, phagocytosis, and opsonization of bacteria in the blood. Filtration of blood involves removal of antibodies, intracellular materials, and destruction of defective cells. During this filtration process, debris and foreign particles, unopsonized bacteria, and parasite-containing erythrocytes are removed, and iron, erythrocytes, and platelets are sequestered. These sequestered cells can be used for response to bleeding or infection.The spleen is also capable of extramedullary hematopoiesis, as some hematopoietic stem cells present during the second trimester remain into adult life.1,2

There are 3 types of asplenia: congenital asplenia, acquired asplenia, and acquired hyposplenia.1 Congenital asplenia is rare and manifests as a reduced spleen size or absence of the spleen. Therefore, the function of the spleen varies from patient to patient. Acquired hyposplenia is the impairment of splenic function related to inflammatory, rheumatologic, or immunologic disorders. In addition to the disorders themselves, some of the pharmacotherapies used to manage these disorders can directly impair the function of the spleen. Acquired asplenia is the predictable loss of function after infarction or surgical removal of the spleen. Indications for surgical splenectomy include trauma, intractable anemia, or symptomatic splenomegaly. Partial splenectomy is an option in some patients, though the ability of the remaining tissue to protect against infections is unclear. Sickle cell anemia is a common cause of splenic atrophy and eventual asplenia. About 22,000 to 25,000 of splenectomies are performed annually in the United States, and close to 1 million people are currently asplenic.3,4

Without a functioning spleen to remove debris and bacteria, risk of infection is a major concern.1,2 B-cell responses which are dependent on T cells occur in the spleen, with formation of IgM and IgG2 antibodies.1 Without these antibodies to polysaccharide antigens, the body’s response against these is greatly impaired. Furthermore, the body’s ability to mount an immune function against polysaccharide encapsulated bacteria is lost. Within 90 days of splenectomy, the relative risk of infection compared to the general population is 10.2% versus 0.6% (odds ratio [OR], 18.1; 95% confidence interval [CI], 14.8 to 22.1).5 Even after a year of splenectomy, the hazard of infection is 2.5 times higher compared to the general population (95% CI, 2.2 to 2.8). Infections caused by encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib) are of particular concern.2 The case-fatality rate of splenectomized patients with sepsis due to S. pneumoniae is 50% to 80%. After splenectomy, patients have an increased risk for hospitalizations due to pneumonia, meningitis, septicemia (rate ratios of 1.9 to 3.4) as well as increased risk for mortality from pneumonia and septicemia (rate ratios of 1.6 to 3.0).4

Prevention of infections

The prevention of severe infection in hospitalized asplenic patients can be achieved with antibiotic or vaccination prophylaxis.1 Because the risk of infection is high within the first 3 months of splenectomy, it is ideal to vaccinate against certain bacteria at least 2 weeks before the procedure, if possible. The 2013 Infectious Diseases Society of America clinical practice guideline for vaccination of the immunocompromised host and the 2019 recommendations from the Advisory Committee on Immunization Practices (ACIP)– agree on the necessity of pneumococcal, Hib, and meningococcal vaccination for asplenic and hyposplenic patients.3,6 Live attenuated influenza vaccine is contraindicated in this patient population.3,7 Compared to the general population, patients with splenectomy require higher antibody concentration to have appropriate protection against S. pneumoniae and Hib.3 All other routine vaccinations are likely effective in this patient population.6 A summary of the recommendations for the administration of these vaccines is in the Table below.

Table. Summary of 2019 vaccination recommendations for adult asplenic and hyposplenic individuals from the Advisory Committee on Immunization Practices.1,7-9

Target pathogen Vaccine (Abbreviation) and recommended schedule Brand name(s)

(Manufacturer)

Dose and administration
Streptococcus  pneumoniae Plain polysaccharide vaccine 23

(PPSV23) x 1 dose in patients 65 years or older (must be at least 5 years after most recent PPSV23)

Pneumovax-23

(Merck Sharp & Dohme)

0.5 mL/dose IM or SC
Pneumococcal conjugate vaccine 13 (PCV13) x 1 dose followed by PPSV23 x 1 dose after 8 weeks, and PPSV23 x 1 dose after 5 years from the last PPSV23 dose Prevnar 13

(Pfizer)

0.5 mL/dose IM
Haemophilus influenzae type b Type B conjugate vaccine

(Hib) x 1 dose if previously not received or at least 14 days before splenectomy

ActHIB

(Sanofi Pasteur)

Hiberix

(Glaxo Smith Kline)

0.5 mL/dose IM
Neisseria meningitidis Meningococcal serogroups A/C/Y/W-135 vaccine (MenACWY) x 2 doses at least 8 weeks apart

Revaccinate every 5 years

Menactra

(Sanofi Pasteur)

Menveo

(Glaxo Smith Kline)

0.5 mL/dose IM
Meningococcal serogroup B vaccine (MenB-4C)a x 2 doses at least 1 month apart Bexsero

(Glaxo Smith Kline)

0.5 mL/dose IM
Meningococcal serogroup B vaccine (MenB-fHbp)a x 3 doses at 0, 1 to 2, and 6 months Trumenba

(Pfizer)

0.5 mL/dose IM
aMenB-4C and MenB-Fhbp are not interchangeable

Abbreviations: IM, intramuscular; SC, subcutaneous.

Pneumococcal vaccination

In the United States, 2 types of pneumococcal vaccines are available: conjugate and polysaccharide vaccines.10,11 Pneumococcal 13-valent vaccine (PCV13) is a pneumococcal conjugate vaccine, which has a polysaccharide attached to a carrier protein. Such structure of vaccine engages helper T cells to stimulate immunogenic memory, and thus, leads to long-term immunity. Pneumococcal polysaccharide 23-valent vaccine (PPSV23) is a polysaccharide vaccine, which contains pure cell wall polysaccharides from bacteria. This type of vaccine mainly stimulates B cells without helper T cells.

The Table shows the recommended schedule for pneumococcal vaccination in patients with asplenia. According to the data from Centers for Disease Control and Prevention (CDC), about 50% of invasive pneumococcal diseases in immunocompromised adults are due to serotypes contained in PCV13 vaccination and about 21% due to serotypes contained only in PPSV23.12 Immunocompromised patients may have reduced response to PPSV23, but the CDC recommends the administration of this vaccine to reduce the risk of invasive pneumococcal disease.11 If the pneumococcal vaccination cannot be administered prior to the splenectomy, then administration should be delayed until functional antibody response returns, at least 14 days after the procedure.3

Pneumococcal vaccine (PCV13 or PPSV23) can be safely given at the same time as inactivated influenza vaccine, but there are no data relating to other vaccinations.13 Concomitant administration of PPSV23 with zoster vaccine may lead to a loss of immune response to zoster vaccine. Ideally, these vaccines should be given at least 4 weeks apart. However, the CDC endorses the administration of both of these vaccines at the same time to limit barriers to vaccination.

Haemophilus influenza type b vaccination

The ACIP does not recommend routine administration of Hib vaccine to the general adult population, but patients with asplenia or hyposplenia should receive Hib vaccination if not vaccinated before.3,8 In the United States, adults with asplenia can receive one of the 2 Hib vaccines: ActHIB or Hiberix.10 Both have the Hib capsular polysaccharide bound to tetanus toxoid. Revaccination is not necessary.

The CDC states that the concomitant administration of Hib vaccine with routine childhood vaccinations is allowed.14 However, the organization does not provide any recommendations regarding concomitant administration with other adult vaccines.

Meningococcal vaccination

There are 2 types of meningococcal vaccines available for this population: recombinant protein and conjugated vaccines.15 Meningococcal recombinant protein vaccines provide protection against only 1 serogroup (serogroup B), and thus, are considered monovalent and are referred to as MenB vaccines. Bexsero and Trumenba are 2 formulations of MenB vaccines. Bexsero consists of Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), factor H binding protein (fHbp), and outer membrane vesicles (OMV), while Trumenba contains 2 variants of fHbp. Conjugate vaccines provide protection against 4 serogroups (A, C, W, and Y) and are denoted as MenACWY. Menactra and Menveo are the available MenACWY vaccines.

Several vaccines can be administered concomitantly with meningococcal vaccines.16 MenACWY vaccines can be administered with tetanus toxoid/reduced diphtheria toxoid/acellular pertussis (Tdap), human papillovirus (HPV), and MenB vaccines. MenB vaccines can be administered with the same vaccines as MenACWY. Co-administration of Menveo with PCV13 is possible, while Menactra may decrease the immune response to PCV13 if co-administered.10 Patients with asplenia should receive PCV13 first due to pneumococcal disease carrying a higher risk in this patient population. The administration of Menactra may follow at least 4 weeks after PCV13 administration.  Providers should use different injection sites if concomitant vaccine administration is necessary.16

Precautions and Contraindications

Pneumococcal, meningococcal, and Hib vaccines are contraindicated if the patient previously experienced a severe allergic reaction such as anaphylaxis upon administration of the vaccine or a component.17-19 In patients who are experiencing symptoms of moderate or severe acute illness regardless of the presence of a fever, these vaccinations may be administered if the benefits outweigh the risks.

Certain vaccines are manufactured with a diphtheria conjugates as the protein carrier.9 MenACWY vaccines are contraindicated in patients who have had a reaction to diphtheria toxoid.  PCV13 is also contraindicated in patients who have had a severe reaction to a diphtheria toxoid-containing vaccine.17 Some vaccinations contain latex in the vial stoppers (PedvaxHIB, Bexsero).20

Adverse effects are possible with pneumococcal, meningococcal, and Hib vaccines. Pain, swelling, or redness may occur in up to 50% of PCV13 recipients, with 8% recipients developing more severe reaction such as tenderness that interferes with limb movement.21 About 30% to 50% of patients receiving PPSV23 may report pain, swelling, or erythema, and most of these symptoms resolve within 48 hours. Adverse events with the Hib vaccine are mild (eg, swelling, redness, pain), uncommon (present in 5% to 30% of recipients), and usually resolve within 12 to 24 hours of administration.22 Common adverse reactions with MenACWY vaccines include fever (17%), headache (16%), injection site erythema (15% to 20%), injection site swelling (14%), and dizziness (13%).23 A higher percentage of patients experience adverse events with MenB vaccines, with over 80% of patients experiencing injection site pain.24,25 Fatigue may be present in 35% to 60% of patients, headache in over 33% of patients, and myalgia in over 35% of patients, depending on the formulation used.

Conclusion

Acquired asplenia or hyposplenia increases an individual’s susceptibility to infections with encapsulated bacteria such as S. pneumoniae, H. influenzae, and N. meningitidis. Therefore, prophylactic measures with immunizations are necessary for this population, and exceptions to the typical dosing schedules for these vaccines are made for individuals with asplenia or hyposplenia.

References

  1. Gilsdorf JR. Infections in asplenic patients. In: Bennet JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Saunders; 2015. https://www.clinicalkey.com. Accessed August 6, 2019.
  2. Longo DL. Enlargement of lymph nodes and spleen. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison's Principles of Internal Medicine. 20th ed. New York, NY: McGraw-Hill; 2018. http://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=192014340. Accessed August 06, 2019.
  3. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-100.
  4. Kristinsson SY, Gridley G, Hoover RN, Check D, Landgren O. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica. 2014;99(2):392-398.
  5. Thomsen RW, Schoonen WM, Farkas DK, et al. Risk for hospital contact with infection in patients with splenectomy: a population-based cohort study. Ann Intern Med. 2009;151(8):546-555.
  6. Altered immunocompetence. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html. Updated July 12, 2017. Accessed August 8, 2019.
  7. Kim DK, Hunter P. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2019. MMWR Morb Mortal Wkly Rep. 2019;68(5):115-118.
  8. Table 2. Recommended adult immunization schedule by medical condition and other indications, United States, 2019. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html. Updated February 5, 2019. Accessed August 8, 2019.
  9. Facts and Comparisons [database online]. New York, NY: Wolters Kluwer, Inc; 2019. https://fco.factsandcomparisons.com/lco/action/home?siteid=5&. Accessed August 8, 2019.
  10. Hammerquist RJ, Messerschmidt KA, Pottebaum AA, Hellwig TR. Vaccinations in asplenic adults. Am J Health Syst Pharm. 2016;73(9):e220-228.
  11. About pneumococcal vaccines. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/about-vaccine.html. Updated December 6, 2017. Accessed August 13, 2019.
  12. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816-819.
  13. Administering pneumococcal vaccines. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/administering-vaccine.html. Updated December 6, 2017. Accessed August 13, 2019.
  14. Administering Hib vaccines. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/hib/hcp/administering-vaccine.html. Updated February 13, 2018. Accessed August 13, 2019.
  15. About meningococcal vaccines. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/mening/hcp/about-vaccine.html. Updated July 26, 2019. Accessed August 13, 2019.
  16. Administering meningococcal vaccines. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/mening/hcp/administering-vaccine.html. Updated July 26, 2019. Accessed August 13, 2019.
  17. Pneumococcal vaccine recommendations. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/recommendations.html. Updated December 6, 2017. Accessed August 13, 2019.
  18. Hib vaccine recommendations. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/hib/hcp/recommendations.html. Updated February 13, 2018. Accessed August 13, 2019.
  19. Meningococcal vaccine recommendations. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/mening/hcp/recommendations.html. Updated July 26, 2019. Accessed August 13, 2019.
  20. Latex in vaccine packaging. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/latex-table.pdf. Updated May 2019. Accessed August 13, 2019.
  21. Pneumococcal disease. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html. Accessed August 13, 2019.
  22. Haemophilus influenzae type b. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/hib.html. Accessed August 13, 2019.
  23. Meningococcal disease. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015. https://www.cdc.gov/vaccines/pubs/pinkbook/mening.html. Accessed August 13, 2019.
  24. Bexsero [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2018.
  25. Trumenba [package insert]. Philadelphia, PA: Pfizer; 2018.

Prepared by:
Janna Afanasjeva, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois At Chicago College of Pharmacy

September 2019

The information presented is current as August 13, 2019. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.

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