Pneumococcal immunization in the elderly and immunocompromised

The Tablet

By Alan Low, BSc.(Pharm.), Pharm. D., RPh, ACPR, FCSHP, CCD
Clinical Associate Professor
Faculty of Pharmaceutical Sciences, UBC

Despite the positive results from studies and demonstrated benefit of immunization against Streptococcus pneumoniae (Sp), people who are at high risk of pneumococcal infection, such as those who are 65 years and older and immunocompromised adults, remain largely unvaccinated. Vaccination rate for pneumococcal infection in 2012 in Canada for people 65 years and older was estimated at 38% when the national target was set at 80% in 2010 by the Public Health Agency of Canada. Even more alarming is the lower rate of vaccination for people with Chronic Medical Conditions (CMC) aged 18-64 years which was estimated at 19%, again with the backdrop of a national target set at 80% vaccination rate for this group.

The bacteria Sp can cause serious and sometimes life-threatening infections such as meningitis, pneumonia and septicemia. Pneumococcal disease is frequent in infancy and the elderly, and the low rate of disease in children is largely because of the routine childhood immunization programs in B.C. and Canada. Pneumococcal disease continues to be a significant problem in the elderly and immunocompromised individuals. One of the main natural reservoirs of Sp is the nasopharynx of humans. Since bacterial transmission can occur easily through respiratory droplets to others, immunity and protection against invasive pneumococcal disease is important and easily attainable through vaccination. Pneumococcal infection can be spread by coughing, sneezing or through saliva with the sharing of drinks and food. Invasive pneumococcal disease may occur when the bacteria spreads to the sinuses, middle ear, or lungs and then may also enter the blood stream, without the immune response required to prevent the infection.

In B.C., the pneumococcal conjugate vaccine (PCV) 7 has been used since 2003 in infant and childhood vaccination programs and has been replaced by PCV 13 in 2010. The PCV 13 (Prevnar 13) vaccine protects against 13 serotypes of Sp (13-valent) and is available as a sterile suspension containing an adjuvant (added to increase the body’s immune response to the vaccine). This preparation has differences to the more commonly known pneumococcal polysaccharide vaccine 23 (PPSV 23), which has been administered to adults, known as Pneumovax 23. The PPSV 23, as the name implies, is aimed at preventing pneumococcal disease from 23 Sp serotypes and is formulated with polysaccharide antigens. The PCV 13 vaccine also contains polysaccharide antigens, and in addition these antigens are covalently linked to a carrier protein, hence the term “conjugated.” Furthermore, it has been reported that polysaccharide vaccines elicit a T cell-independent immune response, and conjugated vaccines elicit a T cell-dependent immune response. This difference offers an advantage for PCV 13 in that it induces immune memory and also reduces colonization of Sp in the nasopharynx. This would indicate that PCV 13 would produce a stronger immune response upon exposure to the bacterium and the duration of immunity would also last longer. With the reduction in colonization in the nasopharynx, the implication is that it may help provide herd immunity or indirect immunity, potentially protecting those individuals who have not been vaccinated.  Moreover, children less than two years of age generally respond poorly to polysaccharide antigens in vaccines, but respond well to polysaccharide antigens conjugated to a carrier protein. This is the reason PCV 7 and now PCV 13 is part of the infant and childhood vaccinations programs across Canada.

In Canada, PCV 7 was first introduced in 2001 followed by PCV 13 in 2010 and guidelines for the administration of this vaccine and others are produced by the National Advisory Committee on Immunization (NACI). NACI is a national expert advisory committee reporting to the Federal Assistant Deputy Minister of Infectious Disease Prevention and Control and makes recommendations for the use of vaccines in humans in Canada.

The CAPiTA tria was a study with about 85,000 adults aged 65 and older who were immunocompetent and did not receive prior pneumococcal vaccine. The subjects were randomized to PCV 13 or placebo administered intramuscularly. In four years of follow up, there was a 46% relative reduction in the first episode of vaccine-type pneumococcal community acquired pneumonia and 45% relative reduction of vaccine-type nonbacteremic and non-invasive pneumococcal pneumonia. With respect to vaccine-type invasive pneumococcal disease, a 75% reduction was reported. There were not enough occurrences of death for an analysis of mortality.

Pharmacists can play an important role in reducing the risk of pneumococcal infections which can lead to severe complications and death by routinely assessing patients who are at high risk and offering to immunize those at risk. These high risk individuals are adults who have CMC, who are immunocompromised or aged 65 years and older (See Table 1). These patients should be offered the option for pneumococcal vaccination and, as appropriate, a discussion which includes the risks and benefits of being vaccinated. With respect to payment and coverage, PPSV 23 is part of the publicly funded vaccine program and although PCV 13 is publicly funded for infants and children, it is not part of the publicly funded adult vaccines in B.C. Many private health plans provide reimbursement for PCV 13 vaccine at some level, sometimes reimbursing for pharmacist initiated vaccinations without requiring a physician’s prescription. This may vary by health benefit plan and carrier.

For patients who are naïve to any type of pneumococcal vaccine, NACI recommends administration of PCV 13 first and then after eight weeks or longer, the administration of PPSV 23.  For people who have received PPSV 23 vaccine in the past, health-care professionals should ensure that one year or more has passed before administering PCV 13 (See Figure 1).  
 

Table 1: NACI recommendations for pneumococcal vaccine in 18 years and older who are immunocompromised and 65 years and older.

NACI recommendations for Hematopoietic stem cell transplantation (HSCT) patients.
Dosing: HSCT recipients should receive a primary series of 3 doses of PNEU-C-13 starting 3-9 months after transplant, after discussion with transplant specialists. The primary series (3 doses) should be administered at least 4 weeks apart, followed by a booster dose of PNEU-P-23 12 to 18 months post transplant (6 to 12 months after the last dose of PNEU-C-13).
Recommend the use of PNEU-C-13 for HSCT recipients given the improved immunogenicity of pneumococcal conjugate vaccines compared to PNEU-P-23 in HSCT recipients. (NACI recommendation A)
NACI recommendations for Human Immunodeficiency Virus (HIV)-positive patients.
Dosing: HIV-positive subjects should receive one dose of PNEU-C-13 followed 8 weeks later by one dose of PNEU-P-23. 
Recommend the use of PNEU-C-13 for HIV-positive patients given the improved efficacy and effectiveness of pneumococcal conjugate vaccine (PNEU-C-7) in HIV-positive subjects.  There is currently no evidence that a PNEU-C-13 booster dose adds any benefit (NACI recommendation A)
Monoarticular/oligoarticular arthritis (brief attacks) NACI recommendation for patients with immunocompromising conditions.
Dosing: These immunocompromised patients should receive one dose of PNEU-C-13 followed 8 weeks later by one dose of PNEU-P-23.
Recommend the use of PNEU-C-13 for subjects with other immunocompromising conditions including: 
Asplenia (anatomical or functional)
Sickle cell disease or other hemoglobinopathies
Congenital immunodeficiencies involving any part of the immune system, including B-lymphocyte (humoral) immunity, T-lymphocyte (cell) mediated immunity, complement system (properdin, or factor D deficiencies), or phagocytic functions 
Immunosuppressive therapy including use of long term corticosteroids, chemotherapy, radiation therapy, post-organ-transplant therapy, biologic and non-biologic immunosuppressive therapies for rheumatologic and other inflammatory diseases. 
Malignant neoplasms including leukemia and lymphoma
Solid organ or islet cell transplant (candidate or recipient).
There is currently no evidence that a PNEU-C-13 booster dose adds any benefit. (NACI recommendation B)
NACI recommendation for patients aged 65 years and older.
Dosing:the use of PNEU-C-13 vaccine followed by PNEU-P-23, for the prevention of CAP and IPD caused by the 13 pneumococcal serotypes included in the conjugate vaccine
Recommend in immunocompetent adults aged 65 years and older not previously immunized against pneumococcal disease,. (NACI Recommendation Grade A).

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