| Pneumococcal infection | |
|---|---|
| Other names | Pneumococcosis |
| Specialty | Respirology,neurology |
Pneumococcal infection is aninfection caused by the bacteriumStreptococcus pneumoniae.[1]
S. pneumoniae is a common member of thebacterial flora colonizing thenose and throat of 5–10% of healthy adults and 20–40% of healthy children.[2] However, it is also a cause of significant disease, being a leading cause ofpneumonia, bacterialmeningitis, andsepsis. TheWorld Health Organization estimates that in 2005, pneumococcal infections were responsible for the death of 1.6 million children worldwide.[3]
Pneumococcal pneumonia represents 15%–50% of all episodes ofcommunity-acquired pneumonia, 30–50% of all cases of acuteotitis media, and a significant proportion ofbloodstream infections and bacterialmeningitis.[4]
As estimated by theWHO, 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.[3]
S. pneumoniae is normally found in thenose and throat of 5–10% of healthy adults and 20–40% of healthy children.[2] 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 surfaceadhesins. This normal colonization can become infectious if the organisms are carried into areas such as theEustachian tube ornasal sinuses where it can causeotitis media andsinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, orsmoking-induced ciliary paralysis might be contributing factors). The organism'spolysaccharide capsule makes it resistant tophagocytosis and if there is no pre-existing anticapsular antibody alveolarmacrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can causebacteremia) and is carried to themeninges, joint spaces,bones, andperitoneal cavity, and may result inmeningitis,brain abscess,septic arthritis, orosteomyelitis.[citation needed]
S. pneumoniae has severalvirulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibitcomplement-mediated opsonization, and it secretes IgA1 protease that will destroy secretoryIgA produced by the body and mediates its attachment to respiratory mucosa.[citation needed]
The risk of pneumococcal infection is much increased in persons with impairedIgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functionalspleen, throughcongenital asplenia,surgical removal of the spleen, orsickle-cell disease predisposes one to a more severe course of infection (overwhelming post-splenectomy infection) and prevention measures are indicated.[citation needed]
People with a compromised immune system, such as those living withHIV, are also at higher risk of pneumococcal disease.[5] 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%.[5]
There is an association between pneumococcal pneumonia andinfluenza. Damage to the lining of the airways (respiratory epithelium) andupper respiratory system caused by influenza may facilitate pneumococcal entry and infection.[6] Influenza also modifies theinnate immune system into a state more accommodating to pneumococcal infections.[7] Most of the deaths in the1918 influenza pandemic were attributable to bacterial infections, especially pneumococcus.[8] There is also a link between pneumococcal infection andrespiratory syncytial virus infection among children.[9]
Other risk factors includesmoking,injection drug use,hepatitis C, andCOPD.[5]
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 withS. pneumoniae.[citation needed]
Depending on the nature of infection an appropriate sample is collected for laboratory identification. Pneumococci are typically gram-positive cocci seen in pairs or chains. When cultured onblood agar plates with addedoptochin antibiotic disk they showalpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic. Pneumococci are also bile soluble. Just like otherstreptococci they arecatalase-negative. AQuellung test can identify specific capsular polysaccharides.[15]
Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionallyfalse-positive. Better results are achieved with rapidimmunochromatography, which has asensitivity (identifies the cause) of 70–80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples but has been applied successfully to other body fluids.[15] Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent.[citation needed]
Due to the importance of disease caused byS. pneumoniae, severalvaccines have been developed to protect against invasive infection. TheWorld Health Organization recommend routine childhood pneumococcal vaccination;[16] it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom,[17] United States,[18] and South Africa.[19]
Throughout history treatment relied primarily onβ-lactam antibiotics. In the 1960s nearly all strains ofS. pneumoniae were susceptible topenicillin, but more recently there has been an increasing prevalence of penicillinresistance especially in areas of highantibiotic use. A varying proportion of strains may also be resistant tocephalosporins,macrolides (such aserythromycin),tetracycline,clindamycin and thefluoroquinolones. Notably, macrolide-resistantS. pneumoniae has been declared a medium-priority pathogen by the WHO due to its growing clinical and public health significance.[20] Penicillin-resistant strains are more likely to be resistant to other antibiotics. Most isolates remain susceptible tovancomycin, though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the medication and concerns of development of vancomycin resistance.[citation needed]
More advanced beta-lactam antibiotics (cephalosporins) are commonly used in combination with other antibiotics to treat meningitis and community-acquired pneumonia. In adults recently developed fluoroquinolones such aslevofloxacin andmoxifloxacin are often used to provide empiric coverage for patients with pneumonia, but in parts of the world where these medications are used to treattuberculosis, resistance has been described.[21]
Susceptibility testing should be routine with empiric antibiotic treatment guided by resistance patterns in the community in which the organism was acquired. There is currently debate as to how relevant the results of susceptibility testing are to clinical outcome.[22][23] There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes.[24]
Resistant pneumococci strains are called penicillin-resistant pneumococci (PRP),[25] penicillin-resistantStreptococcus pneumoniae (PRSP),[26]Streptococcus pneumoniae penicillin resistant (SPPR),[27] or drug-resistantStrepotococcus pneumomoniae (DRSP).[28]
In the 19th century it was demonstrated that immunization ofrabbits with killed pneumococci protected them against subsequent challenge with viable pneumococci.Serum from immunized rabbits or from humans who had recovered from pneumococcal pneumonia also conferred protection. In the 20th century, the efficacy of immunization was demonstrated inSouth African miners.[citation needed]
It was discovered that the pneumococcus's capsule made it resistant to phagocytosis, and in the 1920s it was shown that an antibody specific for capsular polysaccharide aided the killing ofS. pneumoniae. In 1936, a pneumococcal capsular polysaccharide vaccine was used to abort an epidemic of pneumococcal pneumonia. In the 1940s, experiments on capsular transformation by pneumococci first identifiedDNA as the material that carries genetic information.[29]
In 1900 it was recognized that differentserovars of pneumococci exist and that immunization with a given serovar did not protect against infection with other serovars. Since then over ninety serovars have been discovered each with a unique polysaccharide capsule that can be identified by thequellung reaction. Because some of these serovars cause disease more commonly than others it is possible to provide reasonable protection by immunizing with less than 90 serovars; current vaccines contain up to 23 serovars (i.e., it is "23-valent").[citation needed]
The serovars are numbered according to two systems: the American system, which numbers them in the order in which they were discovered, and the Danish system, which groups them according to antigenic similarities.[citation needed]