Why are patients with Sickle Cell Disease (SCD) particularly susceptible to Streptococcus pneumoniae (Strep pneumo) infections?

From the Guidelines

Patients with sickle cell disease are particularly susceptible to Streptococcus pneumoniae infections due to functional asplenia, which can be mitigated with pneumococcal vaccination and prophylactic penicillin. As sickle cell disease progresses, repeated sickling episodes damage the spleen, eventually leading to its fibrosis and loss of function. The spleen plays a crucial role in filtering encapsulated bacteria like Streptococcus pneumoniae from the bloodstream and producing antibodies against these pathogens. Without proper splenic function, these bacteria can multiply unchecked in the bloodstream. Additionally, sickle cell patients often have impaired complement activation and reduced opsonization capacity, further compromising their immune response to pneumococcal infections.

This susceptibility makes pneumococcal vaccination essential for sickle cell patients, including both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1. Children with sickle cell disease should also receive prophylactic penicillin (penicillin V 125mg twice daily for children under 3 years, 250mg twice daily for older children) until at least age 5 to prevent pneumococcal infections, as recommended by the Advisory Committee on Immunization Practices (ACIP) 1. This prophylaxis, combined with appropriate vaccinations, significantly reduces the risk of life-threatening pneumococcal sepsis in these vulnerable patients.

Some key points to consider in the management of sickle cell disease patients include:

• Pneumococcal vaccination with PCV10 or PCV13 is recommended in all non-vaccinated patients 1
• Prophylactic penicillin should be continued for children with SCD to age >5 years, regardless of vaccination with PCV7 1
• Patients with functional asplenia, such as those with sickle cell disease, have a high risk of sepsis caused by pneumococci and should receive PCV10/13 and PPSV-23 vaccination 1
• The efficacy of the PPSV-23 vaccine to prevent IPD has been proven in healthy adults, as well as in immunocompromised patients including AIIRD patients 1

From the Research

Susceptibility to Strep Pneumoniae in Sickle Cell Disease

• Patients with sickle cell disease are at a higher risk of invasive infection due to Streptococcus pneumoniae, with an incidence rate 30-100 times that of a healthy population of the same age 2.
• The major contributor to this increased risk is splenic dysfunction, which impairs the immune system's ability to fight off encapsulated bacteria like Streptococcus pneumoniae 2, 3.
• Other factors that may enhance the risk of infection include abnormalities in immunologic defense mechanisms, such as synthesis of polyclonal IgG and IgM, the alternative complement pathway, opsonic activity, and T and B cell interaction 2.

Role of Vaccination and Prophylaxis

• Current evidence suggests that pneumococcal vaccines have only modest protective efficacy in young patients with sickle cell anemia, and alternative vaccines are required 2.
• Antibiotic prophylaxis has been shown to have a protective effect, but its optimal duration and compliance remain unknown 2.
• Conjugate pneumococcal vaccines have been found to be safe and effective in normal healthy patients, and their use is recommended in people with sickle cell disease 4.

Virulence Factors of Streptococcus pneumoniae

• Streptococcus pneumoniae produces virulence factors such as hydrogen peroxide (H2O2) and pneumolysin, which can cause lung injury and contribute to the development of acute chest syndrome in sickle cell disease patients 5.
• The production of H2O2 by Streptococcus pneumoniae can paradoxically contribute to its virulence, as it can overwhelm the host's antioxidant defenses and cause tissue damage 5.

Clinical Implications

• Invasive pneumococcal disease remains a serious risk in sickle cell disease, despite the use of prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine 6.
• Breakthrough cases of invasive pneumococcal disease may involve non-vaccine serotypes, and can occur after 5 years of age when oral penicillin prophylaxis has been terminated 3.