Pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae. S. pneumoniae is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. However, it is also a cause of significant disease, being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimates that in 2005, pneumococcal infections were responsible for the death of 1.6 million children worldwide.
Infections
Pneumococcal pneumonia represents 15%–50% of all episodes of community-acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bloodstream infections and bacterial meningitis. As estimated by the WHO, in 2005 it killed about 1.6 million children every year worldwide with 0.7–1 million of them being under the age of five. The majority of these deaths were in developing countries.
Pathogenesis S. pneumoniae is normally found in the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day-care centers, military barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organisms are carried into areas such as the Eustachian tube or nasal sinuses where it can cause otitis media and sinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). The organism's polysaccharide capsule makes it resistant to phagocytosis and if there is no pre-existing anticapsular antibody alveolar macrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause bacteremia) and is carried to the meninges, joint spaces, bones, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteomyelitis. S. pneumoniae has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body and mediates its attachment to respiratory mucosa. The risk of pneumococcal infection is much increased in persons with impaired IgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functional spleen, through congenital asplenia, surgical removal of the spleen, or sickle-cell disease predisposes one to a more severe course of infection (overwhelming post-splenectomy infection) and prevention measures are indicated. People with a compromised immune system, such as those living with HIV, are also at higher risk of pneumococcal disease. In HIV patients with access to treatment, the risk of invasive pneumoccal disease is 0.2–1% per year and has a fatality rate of 8%. There is an association between pneumococcal pneumonia and influenza. Damage to the lining of the airways (respiratory epithelium) and upper respiratory system caused by influenza may facilitate pneumococcal entry and infection. Influenza also modifies the innate immune system into a state more accommodating to pneumococcal infections. Most of the deaths in the 1918 influenza pandemic were attributable to bacterial infections, especially pneumococcus. There is also a link between pneumococcal infection and respiratory syncytial virus infection among children. Other risk factors include smoking, injection drug use, hepatitis C, and COPD.
Virulence factors S. pneumoniae expresses different virulence factors on its cell surface and inside the organism. These virulence factors contribute to some of the clinical manifestations during infection with S. pneumoniae.
Polysaccharide capsule—prevents phagocytosis by host immune cells by inhibiting C3b opsonization of the bacterial cells Pneumolysin (Ply)—a 53-kDa pore-forming protein that can cause lysis of host cells and activate complement Autolysin (LytA)—activation of this protein lyses the bacteria releasing its internal contents (i.e., pneumolysin) Hydrogen peroxide—causes damage to host cells (can cause apoptosis in neuronal cells during meningitis) and has bactericidal effects against competing bacteria (Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus) Pili—hair-like structures that extend from the surface of many strains of S. pneumoniae. They contribute to colonization of upper respiratory tract and increase the formation of large amounts of TNF by the immune system during sepsis, raising the possibility of septic shock Choline binding protein A / Pneumococcal surface protein A (CbpA/PspA)—an adhesin that can interact with carbohydrates on the cell surface of pulmonary epithelial cells and can inhibit complement-mediated opsonization of pneumococci Competence for genetic transformation likely plays an important role in nasal colonization fitness and virulence (lung infectivity) Extracellular vesicles (pEVs)—secretory vesicles that carry virulence factors, such as serine-threonine kinase, which, upon internalization by host epithelial cells, phosphorylates Beclin 1, leading to autophagy-mediated degradation of the tight junction protein occludin (OCLN), subsequent disruption of the alveolar epithelial barrier, and dissemination of S. pneumoniae S protein—cell wall peptidoglycan (PG) binding protein that, in response to cell wall damage, coordinates cell wall repair and modification in association with a PG synthase PBP1a and PG deacetylase PgdA to resist host antimicrobials and cell-wall targeting antibiotics
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