Streptococcus pneumoniae, Staphylococcus aureus, and group A Streptococcus pyogenes are the 3 most important bacterial pathogens causing infections in otherwise well children. In 2005, it was estimated that S pneumoniae caused 700,000 to 1 million deaths in children younger than 5 years of age. Most of these children lived in developing countries.
There are 90 immunologically and chemically distinct capsular polysaccharides that determine virulence. Based on antigenic similarities, the 90 types have been grouped into 45 serotypes. Relatively few serotypes cause most disease, which has led to development of polyvalent vaccines.
S pneumoniae can cause infection in almost any tissue or organ. The vast majority of infections in children occur in the middle ear, sinuses, lungs, meninges, and bloodstream. In 2000, the US Food and Drug Administration (FDA) approved and the Advisory Committee on Immunization Practices recommended the heptavalent pneumococcal conjugate vaccine (PCV7) for routine use in infants and young children. While this vaccine had an impressive effect on the incidence of invasive pneumococcal disease in vaccine recipients and the general population, serotype replacement of vaccine serotypes with other strains able to cause invasive disease limited effectiveness and led to the development and release in 2010 of the 13 valent vaccine (PCV13), which included the serotypes that emerged following release of PCV7. In addition, there is a 10 valent vaccine (PCV10), containing 3 of the additional 6 serotypes in PCV13, which is licensed in some countries. Use of pneumococcal conjugate vaccines has been limited in low-income countries where they are most needed.
PATHOGENESIS AND EPIDEMIOLOGY
Invasive pneumococcal disease is preceded by colonization of the nasopharynx, the organism having been acquired through respiratory droplet spread from a colonized individual. Colonization of the nasopharynx typically leads to type-specific immunity and clearance. Capsular polysaccharide facilitates nasopharyngeal colonization and also inhibits phagocytosis of the organisms by neutrophils. Antibodies against capsular polysaccharides are protective; however, pneumococci can undergo capsular switching and evade immunity. Other surface components include choline binding proteins, which promote adherence, and pneumococcal surface protein A (PspA), which inhibits complement deposition and, thus, uptake by phagocytes. Cell wall components such as lipoteichoic acid stimulate the inflammatory response with accumulation of fluid, white blood cells, and cytokines, leading to symptomatology. Pneumolysin is a virulence factor released upon autolysis of the bacteria that is capable of lysing a variety of host cells including red and white blood cells and respiratory epithelial cells.
Bacterial adherence in the respiratory tract and subsequent spread to cause upper and lower respiratory tract infection is facilitated by the presence of viral respiratory pathogens resulting in exposure of muscosal receptors. Bacteremia occurs when colonizing bacteria gain access to the bloodstream. Phosphorylcholine in the cell wall binds to the platelet activating factor receptor. This results in the bacterial uptake and transportation across the cell (epithelial or endothelial), leading to bacterial invasion of the bloodstream. Pneumococci ...