Pneumococcal infection


Pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae S pneumoniae is a common flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children1 However, it is also the cause of significant disease being a leading cause of pneumonia, bacterial meningitis, and sepsis The World Health Organization estimate that in 2005 pneumococcal infections were responsible for the death of 16 million children worldwide2

Contents

  • 1 Infections
  • 2 Pathogenesis
    • 21 Virulence factors
  • 3 Diagnosis
  • 4 Prevention
  • 5 Treatment
  • 6 History
  • 7 References
  • 8 External links

Infectionsedit

Pneumococcal meningitis

S pneumoniae is responsible for 15–50% of all episodes of community acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bacteremia and bacterial meningitis3

As estimated by WHO in 2005 it killed about 16 million children every year worldwide with 07–1 million of them being under the age of five The majority of these deaths were in developing countries2

Pathogenesisedit

S pneumoniae is normally found in the nose and throat of 5–10% of healthy adults and 20–40% of healthy children1 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, splenectomy, or sickle-cell disease predisposes one to a more severe course of infection Overwhelming post-splenectomy infection and prevention measures are indicated see asplenia

People whose immune systems are compromised, such as those living with HIV, are also at higher risk of pneumococcal disease4 In HIV patients with access to treatment, the risk of invasive pneumoccal disease is 02–1% per year and has a fatality rate of 8%4

There is an association between pneumococcal pneumonia and influenza5 Damage to the lining of the airways respiratory epithelium and upper respiratory system caused by influenza may facilitate pneumococcal entry and infection

Other risk factors include smoking, injection drug use, Hepatitis C, and COPD4

Virulence factorsedit

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 ie, 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 aureus67
  • 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 shock8
  • 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 9

Diagnosisedit

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 on blood agar plates with added optochin antibiotic disk they show alpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic Pneumococci are also bile soluble Just like other streptococci they are catalase-negative A Quellung test can identify specific capsular polysaccharides10

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 occasionally false-positive Better results are achieved with rapid immunochromatography, which has a sensitivity 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 fluids10 Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent

Preventionedit

Main article: Pneumococcal vaccine

Due to the importance of disease caused by S pneumoniae several vaccines have been developed to protect against invasive infection The World Health Organization recommend routine childhood pneumococcal vaccination;11 it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom,12 United States,13 and South Africa14

Treatmentedit

Throughout history treatment relied primarily on β-lactam antibiotics In the 1960s nearly all strains of S pneumoniae were susceptible to penicillin, but more recently there has been an increasing prevalence of penicillin resistance especially in areas of high antibiotic use A varying proportion of strains may also be resistant to cephalosporins, macrolides such as erythromycin, tetracycline, clindamycin and the quinolones Penicillin-resistant strains are more likely to be resistant to other antibiotics Most isolates remain susceptible to vancomycin, though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the drug and concerns of development of vancomycin resistance More advanced beta-lactam antibiotics cephalosporins are commonly used in combination with other drugs to treat meningitis and community-acquired pneumonia In adults recently developed fluoroquinolones such as levofloxacin and moxifloxacin are often used to provide empiric coverage for patients with pneumonia, but in parts of the world where these drugs are used to treat tuberculosis resistance has been described15 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 outcome1617 There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes18

Historyedit

In the 19th century it was demonstrated that immunization of rabbits 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 in South African miners

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 of S 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 identified DNA as the material that carries genetic information19

In 1900 it was recognized that different serovars 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 the quellung 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 ie, it is "23-valent"

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

Referencesedit

  1. ^ a b Ryan KJ; Ray CG, eds 2004 Sherris Medical Microbiology 4th ed McGraw Hill ISBN 0-8385-8529-9 
  2. ^ a b WHO 2007 "Pneumococcal conjugate vaccine for childhood immunization--WHO position paper" pdf Wkly Epidemiol Rec Geneva: World Health Organization 82 12: 93–104 
  3. ^ Verma R, Khanna P 2012 Pneumococcal conjugate vaccine: A newer vaccine available in India Hum Vaccin Immunother 89
  4. ^ a b c Siemieniuk, Reed AC; Gregson, Dan B; Gill, M John Nov 2011 "The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study" BMC Infectious Diseases 11 314 PMC 3226630  PMID 22078162 doi:101186/1471-2334-11-314 
  5. ^ Walter ND, Taylor TH, Shay DK, et al 2010 "Influenza Circulation and the Burden of Invasive Pneumococcal Pneumonia during a Non‐pandemic Period in the United States" Clin Infect Dis 50 2: 175–183 PMID 20014948 doi:101086/649208 
  6. ^ Pericone, Christopher D; Overweg, Karin; Hermans, Peter W M; Weiser, Jeffrey N 2000 "Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract" Infect Immun 68 7: 3990–3997 PMC 101678  PMID 10858213 doi:101128/IAI6873990-39972000 
  7. ^ Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M 2006 "Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae" J Bacteriol 188 13: 4996–5001 PMC 1482988  PMID 16788209 doi:101128/JB00317-06 
  8. ^ Barocchi M, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, Hultenby K, Taddei A, Beiter K, Wartha F, von Euler A, Covacci A, Holden D, Normark S, Rappuoli R, Henriques-Normark B 2006 "A pneumococcal pilus influences virulence and host inflammatory responses" Proc Natl Acad Sci USA 103 8: 2857–2862 PMC 1368962  PMID 16481624 doi:101073/pnas0511017103 
  9. ^ Li G, Liang Z, Wang X, Yang Y, Shao Z, Li M, Ma Y, Qu F, Morrison DA, Zhang JR 2016 "Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence" Infect Immun 84 6: 1887–901 PMC 4907133  PMID 27068094 doi:101128/IAI00097-16 
  10. ^ a b Werno AM, Murdoch DR March 2008 "Medical microbiology: laboratory diagnosis of invasive pneumococcal disease" Clin Infect Dis 46 6: 926–32 PMID 18260752 doi:101086/528798 
  11. ^ "Pneumococcal vaccines WHO position paper--2012" PDF Wkly Epidemiol Rec 87 14: 129–44 Apr 6, 2012 PMID 24340399 
  12. ^ "Children to be given new vaccine" BBC News 8 February 2006 
  13. ^ "Pneumococcal Vaccination: Information for Health Care Providers" cdcorg Retrieved 26 July 2016 
  14. ^ "Critical decline in pneumococcal disease and antibiotic resistance in South Africa" NICD Retrieved 20 July 2015 
  15. ^ Group For Enteric; Von Gottberg, A; Klugman, K P; Cohen, C; Wolter, N; De Gouveia, L; Du Plessis, M; Mpembe, R; Quan, V; Whitelaw, A; Hoffmann, R; Govender, N; Meiring, S; Smith, A M; Schrag, S 2008 "Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study" The Lancet 371 9618: 1108–1113 PMID 18359074 doi:101016/S0140-67360860350-5 
  16. ^ Peterson LR 2006 "Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter" Clin Infect Dis 42 2: 224–33 PMID 16355333 doi:101086/497594 
  17. ^ Tleyjeh IM, Tlaygeh HM, Hejal R, Montori VM, Baddour LM 2006 "The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis" Clin Infect Dis 42 6: 788–97 PMID 16477555 doi:101086/500140 
  18. ^ Martínez JA, Horcajada JP, Almela M, et al 2003 "Addition of a Macrolide to a β-Lactam based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia" Clin Infect Dis 36 4: 389–395 PMID 12567294 doi:101086/367541 
  19. ^ Avery OT, Macleod CM, McCarty M 1944 "STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III" J Exp Med 79 2: 137–58 PMC 2135445  PMID 19871359 doi:101084/jem792137 

External linksedit

  • November 2nd: World Pneumonia Day Website
  • Pneumococcal Vaccine Accelerated Development and Introduction Plan


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