What is the pathogenesis and management of pneumococcus serotype 3?

From the Guidelines

Streptococcus pneumoniae serotype 3 is a highly virulent pneumococcal serotype characterized by its thick polysaccharide capsule, which enhances bacterial resistance to phagocytosis and complement-mediated clearance, and its management requires prompt antibiotic therapy and prevention strategies, including pneumococcal vaccination with PCV13 and PPSV23, as recommended by the most recent guidelines 1.

Pathogenesis of Pneumococcus Serotype 3

The pathogenesis of serotype 3 pneumococcus involves colonization of the nasopharynx followed by potential spread to the lower respiratory tract, middle ear, sinuses, or bloodstream. Its mucoid appearance and abundant capsule production contribute to its invasiveness and ability to cause severe pneumonia, bacteremia, and meningitis.

• The capsule of pneumococcus serotype 3 is made of polysaccharides, which is a main virulence factor for pneumococcus 1.
• The pathogenesis of serotype 3 pneumococcus is complex and involves multiple factors, including the ability of the bacteria to colonize the nasopharynx and evade the host's immune system 1.

Management of Pneumococcal Serotype 3 Infections

Management of pneumococcal serotype 3 infections requires prompt antibiotic therapy, typically starting with empiric treatment using ceftriaxone (1-2g IV every 24 hours) or ampicillin (2g IV every 4-6 hours) plus azithromycin (500mg daily) for community-acquired pneumonia.

• For meningitis, high-dose ceftriaxone (2g IV every 12 hours) or cefotaxime (2g IV every 4-6 hours) is recommended 1.
• Treatment should be adjusted based on susceptibility testing, as serotype 3 has shown increasing resistance to antibiotics 1.
• Prevention strategies include pneumococcal vaccination with PCV13 and PPSV23, which both cover serotype 3, though this serotype has demonstrated vaccine escape and lower vaccine effectiveness compared to other serotypes 1.

Prevention Strategies

Prevention strategies for pneumococcal serotype 3 infections include pneumococcal vaccination with PCV13 and PPSV23.

• The conjugate PCV13 vaccine contains purified capsular polysaccharide from 13 serologic strains conjugated to a mutant of diphtheria toxoid (CRM197) 1.
• The polysaccharide vaccine PPSV23 induces antibody production in a T-cell independent manner by acting directly on B cells resulting usually in less efficient antibody production compared to T-cell dependent PCV vaccines 1.
• Patients should be vaccinated with PCV13 (in case of no previous PCV13 vaccination) followed by PCV23 after 2 months or an even longer interval, and PPSV23 vaccination should be repeated in 5-year intervals 1.

From the Research

Capsule of Pneumococcus Serotype 3

• The capsule of pneumococcus serotype 3 is a polysaccharide structure that surrounds the bacteria and plays a critical role in its virulence 2, 3.
• The capsule prevents entrapment in mucus during colonization, traps water to protect against desiccation, can serve as an energy reserve, and protects the bacterium against complement-mediated opsonization and immune cell phagocytosis 2.
• Serotype 3 is one of the most problematic serotypes, with severe clinical manifestations including empyema, bacteremia, cardiotoxicity, and meningitis, and a fatality rate of 30%-47% 2.

Pathogenesis of Pneumococcus Serotype 3

• The capsule of serotype 3 promotes intracellular survival and vascular endothelial cell translocation during invasive pneumococcal disease 4.
• The capsule has antioxidant properties that vary according to serotype, and serotype 3 has been shown to have a high level of resistance to oxidative stress-mediated killing 4.
• The capsule also enhances the escape rate of internalized pneumococci and promotes translocation across vascular endothelial cells 4.

Management of Pneumococcus Serotype 3

• The current pneumococcal conjugate vaccine (PCV13) is less effective against serotype 3, and new strategies are needed to prevent and treat serotype 3 infections 5.
• Human monoclonal antibodies to pneumococcal capsular polysaccharide 3 have been isolated and characterized, and have shown promise in reducing nasopharyngeal colonization and prolonging survival in mouse models 5.
• The development of antibody-based therapies and next-generation vaccines for serotype 3 is an active area of research, and may provide new tools for preventing and treating serotype 3 infections 5.